Electrodiagnostic testing (electroretinograms, ERGs, which record activity within the retina and visual evoked potentials, VEPs, which record activity through the postretinal pathways) can be used to estimate visual potential. Visual stimuli are presented, and the child’s physiological response is evaluated. The level of activity is compared to normative data to provide an indication of the child’s visual potential.
NATIONAL STUDY OF PRIMARY INTRAOCULAR LENS IMPLANTATION IN CHILDREN ≤2 YEARS OLD WITH CONGENITAL AND INFANTILE CATARACT AMEENAT OLUFUNMILOLA SOLEBO SUBMISSION OF THESIS FOR THE DEGREE OF DOCTORATE OF PHILOSOPHY UNIVERSITY COLLEGE LONDON UNIVERSITY OF LONDON 2011 I, Ameenat Olufunmilola Solebo, confirm that the work presented in this thesis is my own Where information has been derived from other sources, I confirm that this has been indicated in the thesis ABSTRACT Cataract is a potentially reversible cause of childhood blindness which is responsible for at least 15% of the world’s blind children Primary intraocular lens (IOL) implantation is the most important recent innovation in the management of childhood cataract, and has been widely adopted despite unanswered questions regarding best practice, visual benefits and adverse outcomes In order to answer these questions, an epidemiological study was undertaken through systematic, standardised data collection through a national clinical network, the British Isles Congenital Cataract Interest Group At the time of submitting this thesis, data are available for 236 children IOL implantation was undertaken in the majority of children over months old, but aphakia was the preferred option for younger children, due in part to the higher than anticipated frequency of other ocular anomalies Overall primary IOL implantation conferred no visual benefit for children with unilateral cataract, but may be associated with better visual outcome following bilateral cataract surgery, whilst increasing the risk of the need for further surgical procedures under general anaesthetic, which may adversely impact on future cognitive development 16% of all children developed glaucoma during the first postoperative year with age at surgery being the most significant factor The potential eventual burden of aphakic and pseudophakic glaucoma is considerable, and these findings should encourage debate about the balance between the risk of amblyopia and the risk of glaucoma, as well as future research on this blinding complication Refractive planning and outcome in early life pseudophakia is highly variable There is a pressing need for standardisation of refractive planning and continuous national monitoring of refractive outcomes, similar to that which exists in adult cataract surgical practice Follow up studies of this unique inception cohort will provide further information on longer term outcomes and their impact on educational and personal development ACKNOWLEDGEMENTS This work would not be possible without the support of the families of the recruited children, and I am very grateful to them for their generosity during what was, for them, a difficult time I owe my sponsors, primarily the Ulverscroft Foundation a great deal of thanks for allowing me to undertake this research and to take advantage of the excellent research training available through UCL Institute of Child Health and the wider UCL environment I should also like to thank the NIHR Biomedical Research Centre for support I am grateful for the support and work of the members of the British Isles Congenital Interest Group, particularly those who piloted the draft study documentation, helped us to recruit children, and who collected data As my supervisor’s supervisor said, if you want something done, ask a busy person And I have been incredibly wise in my choice of supervisors Professor Rahi is all that one could wish for as a manager, a colleague, and a role model – insightful (laser beam gaze!), an effective communicator (able to synthesise complex research themes with a single bound!) and approachable Ms Russell-Eggitt has been consistently generous with her time, her knowledge and her supportive spirit, and has helped me to maintain the link between this study and the study participants – the children and their families I would like to thank the clinical and research staff at the recruiting hospitals, particularly the clinical staff at the Manchester Royal Eye Hospital, Birmingham Children’s Hospital, Leicester Royal Infirmary and of course Great Ormond Street Hospital I am grateful for the input of Dr Mario Cortina Borja and Dr Rachel Knowles, my examiners for the PhD upgrade The staff at the MRC Centre of Epidemiology and Biostatistics have played a vital role in my development as an academic: I would like in particular to thank Clare Thorne and Clare Townsend (my ex-neighbours) and Phillippa Cumberland and Val Tadic (my vision group colleagues) for their support and for all the chocolate I’ll finish off by thanking my friends and family for their support (thank you for the story about the mother turtle and her slow, determined and eventually successful attempts to bury her eggs on a beach in Cyprus, Senay) and their understanding of my necessary neglect of them Sorry Mark – but it was worth it, no? CONTENTS Page INTRODUCTION 19 BACKGROUND 20 2.1 The anatomy and development of the eye and visual system 20 2.1.a The anatomy and pre-natal development of the lens 20 2.1.b The anatomy and development of the anterior and posterior segments 23 2.1.c The growth and development of the globe in childhood 25 2.1.d Emmetropisation 26 2.1.e The visual pathways 29 2.1.f Summary 29 2.2 Vision and visual impairment 30 2.2.a Normal visual function 31 2.2.b The development of vision 35 2.2.c Assessing vision in childhood 39 2.2.d Visual impairment and blindness 44 2.2.e Summary 45 2.3 Congenital and infantile cataract 46 2.3.a Incidence of congenital and infantile cataract in the United Kingdom 46 2.3.b The global burden of congenital and infantile cataract 47 2.3.c Aetiology of congenital and infantile cataract 49 2.3.d Phenotypic classification of cataract 51 2.3.e The natural history of congenital and infantile cataract 57 2.3.f The prevention of childhood cataract blindness in the United Kingdom 57 2.3.g Surgical management of congenital and infantile cataract 60 2.3.h Visual (re)habilitation following surgical management 65 2.3.i Summary 68 2.4 Outcomes following congenital and infantile cataract surgery69 2.4.a Evaluating the existing evidence on outcomes 69 2.4.b Visual outcomes following congenital and infantile cataract surgery 73 2.4.c Early post-operative complications of congenital and infantile cataract surgery 78 2.4.d Late post-operative complications of congenital and infantile cataract surgery 80 2.4.e Refractive change following surgery 89 2.4.f Summary 90 2.5 Primary intraocular lens implantation 91 2.5.a The issues surrounding surgical planning for IOL implantation in children versus implantation in adults 93 2.5.b Post-operative visual re(habilitation) 98 2.5.c Visual outcomes following primary IOL implantation in children ≤2 years old 99 2.5.d Adverse outcomes following primary IOL implantation in children ≤2 years old 102 The adoption of paediatric IOL implantation 105 2.5.e Summary 106 2.6 Epidemiological investigation into outcomes following cataract surgery in children under 2: methodological issues 107 2.6.a Rare diseases and rarer outcomes: the challenges of chance, bias and confounding 107 2.6.b Identifying cases 109 2.6.c Statistical analysis of hierarchical data 113 2.6.d Investigating outcomes following intervention in early childhood 114 AIMS 115 METHODS 117 4.1 Introduction 118 4.2 National survey of current practice of primary intraocular lens implantation in children under years old 118 4.2.a Introduction 118 4.2.b Methods 119 4.2.c Statistical analysis 120 4.2.d Results 120 4.2.e Discussion 124 4.3 Establishment and maintenance of the surveillance network125 4.4 Case definition 125 4.5 Case identification and ascertainment through the BCCIG reporting base 126 4.6 Recruitment and consent 126 4.7 Data collection 128 4.7.a Data collection instruments 128 4.7.b Data collection process 130 4.8 Ethics and research governance 132 4.8.a Ethics approval 132 4.8.b Research governance approval 132 4.9 Data management 133 4.9.a Data protection 133 4.9.b Data validation 133 4.9.c Database design 133 4.9.d Data entry 133 4.9.e Data coding: the creation of variables for analysis 135 4.10 Analysis 142 4.10.a Visual outcome 143 4.10.b Per and post-operative events 145 4.11 Identification of cases of cataract surgery and intraocular lens implantation in children under years old in the United Kingdom using the National statistical database 147 4.11.a Identification of eligible codes 147 4.11.b Data request 147 RESULTS 149 5.1 Introduction 150 5.2 Case ascertainment and recruitment 151 5.2.a Distribution of recruiting centres 151 5.2.b Case notification 153 5.2.c Consent and recruitment to study 153 5.3 Data collection 156 5.4 Comparison of IOLunder2 United Kingdom ascertainment with national databases of hospital activity 157 5.5 Descriptive analysis 159 5.5.a Demographic characteristics of the study population 159 5.5.b Pre-operative clinical characteristics 164 5.5.c Age at diagnosis of cataract 186 5.5.d Age at surgery 188 5.5.e Cited exclusion criteria for primary IOL implantation 191 5.5.f Surgical management 193 5.5.g Per operative events 203 5.6 Completeness of post-operative data collection 206 5.7 Visual rehabilitation following cataract surgery 207 5.7.a Refractive correction 207 Occlusion and other visual penalisation 211 5.7.b Summary 213 5.8 Visual outcomes at one year following surgery 214 5.8.a Outcomes following surgery for bilateral cataract 214 5.8.b Outcomes following surgery for unilateral cataract 220 5.8.c Factors associated with visual outcome 223 5.9 Adverse per operative events 237 5.9.a Bilateral cataract 237 5.9.b Unilateral cataract 241 5.10 Adverse outcomes at one year following surgery 244 5.10.a Glaucoma 244 5.10.b Visual axis opacity 255 5.10.c Other adverse events 268 5.11 Refractive outcomes following primary IOL implantation 270 5.11.a Prediction error 270 DISCUSSION 279 6.1 Summary of key findings 280 6.2 Ascertainment of children undergoing cataract surgery in the first two years of life 283 6.2.a Incidence of surgery for congenital and infantile cataract surgery for children ≤2 years old in the UK 283 6.2.b The role of active surveillance in the ascertainment of rare ophthalmic disorders 285 6.3 Prospective studies of disease management - the measurement effect 287 6.3.a Standardisation of clinical records in response to the study 287 6.3.b Standardisation of clinical practice in response to the study 288 6.4 Ocular co-morbidity in children undergoing cataract surgery aged ≤2 years in the British Isles 290 6.4.a Microphthalmos and microcornea 290 6.4.b Persistent fetal vasculature 294 6.5 Practice of IOL implantation in children aged