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 1 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. 2 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 6 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. 3 Follow up studies of this unique inception cohort will provide further information on longer term outcomes and their impact on educational and personal development.
4 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. 5 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? 6 CONTENTS Page 1. The anatomy and development of the eye and visual system 20 2. The anatomy and pre-natal development of the lens 20 2. The anatomy and development of the anterior and posterior segments 23 2.
The growth and development of the globe in childhood 25 2. The visual pathways 29 2. Vision and visual impairment. Normal visual function 31 2.
The development of vision 35 2. Assessing vision in childhood 39 2. Visual impairment and blindness 44 2. Congenital and infantile cataract.
Incidence of congenital and infantile cataract in the United Kingdom 46 2. The global burden of congenital and infantile cataract 47 2. Aetiology of congenital and infantile cataract 49 2. Phenotypic classification of cataract 51 2.
The natural history of congenital and infantile cataract 57 2. The prevention of childhood cataract blindness in the United Kingdom 57 2. Surgical management of congenital and infantile cataract 60 2. Visual (re)habilitation following surgical management 65 2.
Outcomes following congenital and infantile cataract surgery69 2. Evaluating the existing evidence on outcomes 69 2. Visual outcomes following congenital and infantile cataract surgery 73 2. Early post-operative complications of congenital and infantile cataract surgery 78 2.
Late post-operative complications of congenital and infantile cataract surgery 80 2. Refractive change following surgery 89 2. Primary intraocular lens implantation. The issues surrounding surgical planning for IOL implantation in children versus implantation in adults 93 2.
Post-operative visual re(habilitation) 98 2. Visual outcomes following primary IOL implantation in children ≤2 years old 99 2. Adverse outcomes following primary IOL implantation in children ≤2 years old 102 The adoption of paediatric IOL implantation 105 7 2. Epidemiological investigation into outcomes following cataract surgery in children under 2: methodological issues.
Rare diseases and rarer outcomes: the challenges of chance, bias and confounding 107 2. Statistical analysis of hierarchical data 113 2. Investigating outcomes following intervention in early childhood 114 3. National survey of current practice of primary intraocular lens implantation in children under 2 years old.
Establishment and maintenance of the surveillance network125 4. Case identification and ascertainment through the BCCIG reporting base. Recruitment and consent. Data collection instruments 128 4.
Data collection process 130 4. Ethics and research governance. Research governance approval 132 4. Data coding: the creation of variables for analysis 135 4.
Per and post-operative events 145 4. Identification of cases of cataract surgery and intraocular lens implantation in children under 2 years old in the United Kingdom using the National statistical database. Identification of eligible codes 147 4. Case ascertainment and recruitment.
Distribution of recruiting centres 151 5. Consent and recruitment to study 153 5. Comparison of IOLunder2 United Kingdom ascertainment with national databases of hospital activity. Demographic characteristics of the study population 159 5.
Pre-operative clinical characteristics 164 5. Age at diagnosis of cataract 186 5. Age at surgery 188 5. Cited exclusion criteria for primary IOL implantation 191 5.
Per operative events 203 5. Completeness of post-operative data collection. Visual rehabilitation following cataract surgery. Refractive correction 207 Occlusion and other visual penalisation 211 5.
Visual outcomes at one year following surgery. Outcomes following surgery for bilateral cataract 214 5. Outcomes following surgery for unilateral cataract 220 5. Factors associated with visual outcome 223 5.
Adverse per operative events. Adverse outcomes at one year following surgery. Visual axis opacity 255 5. Other adverse events 268 5.
Refractive outcomes following primary IOL implantation. Summary of key findings. Ascertainment of children undergoing cataract surgery in the first two years of life. Incidence of surgery for congenital and infantile cataract surgery for children ≤2 years old in the UK 283 6.
The role of active surveillance in the ascertainment of rare ophthalmic disorders 285 6. Prospective studies of disease management - the measurement effect 287 6. Standardisation of clinical records in response to the study 287 6. Standardisation of clinical practice in response to the study 288 6.
Ocular co-morbidity in children undergoing cataract surgery aged ≤2 years in the British Isles. Microphthalmos and microcornea 290 6. Persistent fetal vasculature 294 9 6. Practice of IOL implantation in children aged <2yrs.
Sources of bias 296 6. Interpretation of findings 297 6. Comparison of ascertainment through central NHS databases and through active surveillance. Sources of bias 299 6.
Interpretation of findings 299 6. Parental willingness to participate in clinical research. Visual outcomes following surgery with and without primary IOL implantation. Glaucoma following surgery with and without primary IOL implantation.
Sources of bias 309 6. Interpretation of findings 310 6. Visual axis opacity following surgery with and without primary IOL implantation. Sources of bias 314 6.
Interpretation of findings 314 6. Accuracy of refractive planning in children ≤2 yrs old. Sources of bias 318 6. Interpretation of findings 318 6.
Future directions of investigations into outcomes within the IOLu2 cohort. Visual outcome following bilateral cataract surgery 321 6. Visual outcome following unilateral cataract surgery 323 6. APPENDICES 353 Appendix A: Aphakic and pseudophakic glaucoma following paediatric cataract surgery.
353 Appendix B: Members of the British Isles Congenital Cataract Interest Group364 Appendix C: Cataract surgery and primary intraocular lens implantation in children ≤2 years old in the United Kingdom and Ireland: findings of a national survey. 366 10 Appendix D: National study of primary IOL implantation in children ≤2 years old (IOLunder2 study) notification forms. 371 Appendix E: IOLunder2 study data collection instruments. 372 Appendix F: IOLunder2 study parental / guardian information sheets and consent form.
385 Appendix G: Hospital specific per operative data collection proforma 391 Appendix H: Four by four data tables. 394 Appendix I: Pre operative visual function:. 396 Appendix J: Biometric data. 398 Appendix K: Flowcharts of surgical procedures undertaken in operated eyes 399 Appendix L: Description of variables used in statistical analyses of outcome.
401 Appendix M: Correlations between factors of interest with regards to visual, refractive and adverse outcome. 404 Appendix N: Search terms for literature review reported within background chapter. 414 11 Index of boxes Page Box 1. The phases of plasticity which define the sensitive period………………36 Box 2.
Age related definition of microphthalmos…………………………………53 Box 3. The British Infantile and Childhood Glaucoma study group definition of glaucoma………………………………………. Differing definitions of glaucoma within the existing literature.93 Index of figures Figure 1. Anatomy of the eye, shown in sagittal (vertical) section.
Cross section through the lens. The fetal intraocular vasculature. Postnatal growth of the globe. Changing refractive (focusing) state with globe elongation.
Visual maturation in childhood showing the rapid improvement in the first year of life. Preferential looking tests. The process of recruitment and data collection. Distribution of the recruiting centres, with a colour code for the number of children identified by the centre during the 2009/2010 study period.
Case ascertainment and recruitment flow chart. Recruitment and data collection across the collaborating hospitals. Interocular axial length difference in children with unilateral cataract. Manifestations of persistent fetal vasculature in individual children with bilateral cataract.
Manifestations of persistent fetal vasculature in individual children with unilateral cataract. Venn diagrammatic scale representation of distribution of systemic disorders and ocular abnormalities. Age at diagnosis of bilateral and unilateral cataract: cumulative proportion graph with age categorised into clinically relevant groups .