Ophthalmology
Volume 123, Number 1, January 2016
context may be used to confirm the pathogenicity of putative disease causing variants. Many patients found to have metabolic disorders were developmentally delayed or had other significant systemic disorders. Although this is the group of patients that would benefit most from genetic testing, it should be noted that otherwise healthy children also benefit from this testing, as the ability to identify multisystemic disorders presymptomatically can allow prompt treatment. We predict that the identification of more mutations underlying this group of disorders will expand and establish phenotypic spectra and allow a better understanding of disease pathogenesis and prognosis.
RACHEL L. GILLESPIE, PHD1 JILL URQUHART, PHD1 BEVERLEY ANDERSON, MSC1 SIMON WILLIAMS, PHD2 SARAH WALLER, PHD2 JANE ASHWORTH, FRCOPHTH3 SUSMITO BISWAS, FRCOPHTH3 SIMON JONES, MRCPCH2 FIONA STEWART, FRCPCH4 I. CHRISTOPHER LLOYD, FRCOPHTH3 JILL CLAYTON-SMITH, MD, FRCP1,2 GRAEME C.M. BLACK, DPHIL, FRCOPHTH1,2 1 Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Saint Mary’s Hospital, Manchester, UK; 2Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, MAHSC, Saint Mary’s Hospital, Manchester, UK; 3 Manchester Royal Eye Hospital, Manchester Academic Health Science Centre, The University of Manchester, Central Manchester Foundation Trust, Manchester, UK; 4Northern Ireland Regional Genetics Service (NIRGS), Belfast City Hospital, Belfast, UK
Financial Disclosure(s): The authors made the following disclosures: S.B.: Fees e Raptor pharmaceuticals, Novartis Pharmaceuticals outside the submitted work. J.A.: Grants and fees e Biomarin Europe Ltd outside of the submitted work. Funded by Fight for Sight, grant no. 1831. The authors also acknowledge the support of the Manchester Academic Health Science Centre and the Manchester National Institute for Health Research Biomedical Research Centre. The funding organization had no role on the design or conduct of this research. Author Contributions: Conception and design: Gillespie, Lloyd, Black Analysis and interpretation: Gillespie, Urquhart, Anderson, Williams, Waller, Jones, Stewart, Lloyd, Clayton-Smith, Black Data collection: Gillespie, Urquhart, Anderson, Williams, Waller, Ashworth, Biswas, Stewart, Lloyd, Clayton-Smith Overall responsibility: Gillespie, Urquhart, Anderson, Williams, Waller, Jones, Stewart, Lloyd, Clayton-Smith, Black Correspondence: Graeme C.M. Black, DPhil, FRCOphth, Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, MAHSC, 6th floor- Saint Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK. E-mail: [email protected].
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References 1. Rahi JS, Dezateux C, British Congenital Cataract Interest Group Measuring and interpreting the incidence of congenital ocular anomalies: lessons from a national study of congenital cataract in the UK. Invest Ophthalmol Vis Sci 2001;42:1444–8. 2. Gillespie RL, O’Sullivan J, Ashworth J, et al. Personalized diagnosis and management of congenital cataract by next-generation sequencing. Ophthalmology 2014;121:2124–37. 31-2. 3. Ebberink MS, Koster J, Visser G, et al. A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11 beta gene. J Med Genet 2012;49:307–13. 4. Ho AC, Fung CW, Siu TS, et al. Lathosterolosis: a disorder of cholesterol biosynthesis resembling Smith-Lemli-Opitz syndrome. JIMD Rep 2014;12:129–34. 5. Flatt JF, Guizouarn H, Burton NM, et al. Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome. Blood 2011;118:5267–77.
Cognitive Function and Subfoveal Choroidal Thickness: The Beijing Eye Study Since the landmark study by Spaide et al1 described the enhanced depth imaging mode of spectral-domain optical coherence tomography to visualize the choroid, choroidal thickness has been examined intensively in recent investigations. None of the preceding studies examined whether neurologic diseases were associated with an abnormal choroidal thickness, although the choroidal blood vessels predominantly influencing choroidal thickness can be regarded as an extracranial part of the intracranial cerebral vascular system. We therefore assessed whether subfoveal choroidal thickness (SFCT) is associated with cognitive function as a measure of brain function, and vice versa, whether cognitive function is associated with SFCT. The population-based Beijing Eye Study 2011 was approved by the Medical Ethics Committee of the Beijing Tongren Hospital. Out of an eligible population of 4403 individuals with an age of 50 years, 3468 individuals (78.8%) participated.2 Using the enhanced depth mode of optical coherence tomography (Spectralis, Heidelberg Engineering Co., Heidelberg, Germany), SFCT was measured. Only the right eye of each study participant was assessed. Using fundus photographs, we assessed the degree of fundus tessellation, defined as variation in the visibility of the large choroidal vessels in the region of the macula and optic nerve head.3 It was differentiated into 3 grades. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung self-rated depression scale.4 The total score of depression symptoms was converted to a 100-point scale. Cognitive function was assessed using the Mini Mental Status Examination scale.5 Statistical analysis was carried out using a statistical software package (SPSS for Windows, version 22.0, IBM-SPSS, Chicago, IL). We presented 95% CI. All P values were 2-sided and considered significant when
Volume 123, Number 1, January 2016
context may be used to confirm the pathogenicity of putative disease causing variants. Many patients found to have metabolic disorders were developmentally delayed or had other significant systemic disorders. Although this is the group of patients that would benefit most from genetic testing, it should be noted that otherwise healthy children also benefit from this testing, as the ability to identify multisystemic disorders presymptomatically can allow prompt treatment. We predict that the identification of more mutations underlying this group of disorders will expand and establish phenotypic spectra and allow a better understanding of disease pathogenesis and prognosis.
RACHEL L. GILLESPIE, PHD1 JILL URQUHART, PHD1 BEVERLEY ANDERSON, MSC1 SIMON WILLIAMS, PHD2 SARAH WALLER, PHD2 JANE ASHWORTH, FRCOPHTH3 SUSMITO BISWAS, FRCOPHTH3 SIMON JONES, MRCPCH2 FIONA STEWART, FRCPCH4 I. CHRISTOPHER LLOYD, FRCOPHTH3 JILL CLAYTON-SMITH, MD, FRCP1,2 GRAEME C.M. BLACK, DPHIL, FRCOPHTH1,2 1 Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Saint Mary’s Hospital, Manchester, UK; 2Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, MAHSC, Saint Mary’s Hospital, Manchester, UK; 3 Manchester Royal Eye Hospital, Manchester Academic Health Science Centre, The University of Manchester, Central Manchester Foundation Trust, Manchester, UK; 4Northern Ireland Regional Genetics Service (NIRGS), Belfast City Hospital, Belfast, UK
Financial Disclosure(s): The authors made the following disclosures: S.B.: Fees e Raptor pharmaceuticals, Novartis Pharmaceuticals outside the submitted work. J.A.: Grants and fees e Biomarin Europe Ltd outside of the submitted work. Funded by Fight for Sight, grant no. 1831. The authors also acknowledge the support of the Manchester Academic Health Science Centre and the Manchester National Institute for Health Research Biomedical Research Centre. The funding organization had no role on the design or conduct of this research. Author Contributions: Conception and design: Gillespie, Lloyd, Black Analysis and interpretation: Gillespie, Urquhart, Anderson, Williams, Waller, Jones, Stewart, Lloyd, Clayton-Smith, Black Data collection: Gillespie, Urquhart, Anderson, Williams, Waller, Ashworth, Biswas, Stewart, Lloyd, Clayton-Smith Overall responsibility: Gillespie, Urquhart, Anderson, Williams, Waller, Jones, Stewart, Lloyd, Clayton-Smith, Black Correspondence: Graeme C.M. Black, DPhil, FRCOphth, Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, MAHSC, 6th floor- Saint Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK. E-mail: [email protected].
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References 1. Rahi JS, Dezateux C, British Congenital Cataract Interest Group Measuring and interpreting the incidence of congenital ocular anomalies: lessons from a national study of congenital cataract in the UK. Invest Ophthalmol Vis Sci 2001;42:1444–8. 2. Gillespie RL, O’Sullivan J, Ashworth J, et al. Personalized diagnosis and management of congenital cataract by next-generation sequencing. Ophthalmology 2014;121:2124–37. 31-2. 3. Ebberink MS, Koster J, Visser G, et al. A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11 beta gene. J Med Genet 2012;49:307–13. 4. Ho AC, Fung CW, Siu TS, et al. Lathosterolosis: a disorder of cholesterol biosynthesis resembling Smith-Lemli-Opitz syndrome. JIMD Rep 2014;12:129–34. 5. Flatt JF, Guizouarn H, Burton NM, et al. Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome. Blood 2011;118:5267–77.
Cognitive Function and Subfoveal Choroidal Thickness: The Beijing Eye Study Since the landmark study by Spaide et al1 described the enhanced depth imaging mode of spectral-domain optical coherence tomography to visualize the choroid, choroidal thickness has been examined intensively in recent investigations. None of the preceding studies examined whether neurologic diseases were associated with an abnormal choroidal thickness, although the choroidal blood vessels predominantly influencing choroidal thickness can be regarded as an extracranial part of the intracranial cerebral vascular system. We therefore assessed whether subfoveal choroidal thickness (SFCT) is associated with cognitive function as a measure of brain function, and vice versa, whether cognitive function is associated with SFCT. The population-based Beijing Eye Study 2011 was approved by the Medical Ethics Committee of the Beijing Tongren Hospital. Out of an eligible population of 4403 individuals with an age of 50 years, 3468 individuals (78.8%) participated.2 Using the enhanced depth mode of optical coherence tomography (Spectralis, Heidelberg Engineering Co., Heidelberg, Germany), SFCT was measured. Only the right eye of each study participant was assessed. Using fundus photographs, we assessed the degree of fundus tessellation, defined as variation in the visibility of the large choroidal vessels in the region of the macula and optic nerve head.3 It was differentiated into 3 grades. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung self-rated depression scale.4 The total score of depression symptoms was converted to a 100-point scale. Cognitive function was assessed using the Mini Mental Status Examination scale.5 Statistical analysis was carried out using a statistical software package (SPSS for Windows, version 22.0, IBM-SPSS, Chicago, IL). We presented 95% CI. All P values were 2-sided and considered significant when
