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1. Cohort profile: rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

Author

Martin McKibbin, Tariq Aslam, Sarah Barman, Jenny Barrett, Paul Bishop, Roxana Carare, Usha Chakravarthy, Michelle Chan, Alexander Day, Parul Desai, Bal Dhillon, Andrew Dick, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John Gallacher, Jane Gibson, Jeremy Guggenheim, Chris Hammond, Alison Hardcastle, Simon Harding, Ruth Hogg, Pirro Hysi, Anthony Khawaja, Gerassimos Lascaratos, Andrew Lotery, Phil Luthert, Tom Macgillivray, Sarah Mackie, Bernadette Mcguinness, Gareth Mckay, Tony Moore, James Morgan, Eoin O’sullivan, Chris Owen, Praveen Patel, Euan Paterson, Axel Petzold, Alicja Rudnicka, Paul J Foster, Naomi Allen, Peng Tee Khaw, Praveen J Patel, Konstantinos Balaskas, Richard Oram, Robert Luben, Tasanee Braithwaite, Graeme Black, Christopher G Owen, Zihan Sun, David Garway-Heath, Thomas Littlejohns, Simon Sheard, Sharon Chua, Pearse Keane, Denize Atan, Savita Madhusudhan, and Alexander Doney

Subjects
Medicine
Abstract

Purpose The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study.Participants UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40–69 enrolled in 2006–2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs.Findings to date UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes.Future plans The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022–2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

Published
2023
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2. Real-Time Monitoring Platform for Ocular Drug Delivery

Author

Sahar Awwad, Nkiruka Ibeanu, Tianyang Liu, Angeliki Velentza-Almpani, Nerisha Chouhan, Stavros Vlatakis, Peng Tee Khaw, Steve Brocchini, and Yann Bouremel

Subjects
ocular, ophthalmology, automation, real-time monitoring, concentration probes, saccades, Pharmacy and materia medica, RS1-441
Abstract

Real-time measurement is important in modern dissolution testing to aid in parallel drug characterisation and quality control (QC). The development of a real-time monitoring platform (microfluidic system, a novel eye movement platform with temperature sensors and accelerometers and a concentration probe setup) in conjunction with an in vitro model of the human eye (PK-Eye™) is reported. The importance of surface membrane permeability when modelling the PK-Eye™ was determined with a “pursing model” (a simplified setup of the hyaloid membrane). Parallel microfluidic control of PK-Eye™ models from a single source of pressure was performed with a ratio of 1:6 (pressure source:models) demonstrating scalability and reproducibility of pressure-flow data. Pore size and exposed surface area helped obtain a physiological range of intraocular pressure (IOP) within the models, demonstrating the need to reproduce in vitro dimensions as closely as possible to the real eye. Variation of aqueous humour flow rate throughout the day was demonstrated with a developed circadian rhythm program. Capabilities of different eye movements were programmed and achieved with an in-house eye movement platform. A concentration probe recorded the real-time concentration monitoring of injected albumin-conjugated Alexa Fluor 488 (Alexa albumin), which displayed constant release profiles. These results demonstrate the possibility of real-time monitoring of a pharmaceutical model for preclinical testing of ocular formulations.

Published
2023
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3. Translating Minimally Invasive Glaucoma Surgery Devices

Author

Richard M.H. Lee, Yann Bouremel, Ian Eames, Steve Brocchini, and Peng Tee Khaw

Subjects
Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270
Abstract

Glaucoma is the leading cause of irreversible blindness with over 70 million people affected worldwide. The surgical management of glaucoma aims to lower intraocular pressure by increasing aqueous outflow facility. The latest manufacturing techniques have allowed for the development of a number of novel implantable devices to improve safety and outcomes of glaucoma surgery. These are collectively referred to as minimally invasive glaucoma surgery (MIGS) devices and are among the smallest devices implanted in the human body. This review discusses the design criterion and constraints as well as the user requirements for MIGS devices. We review how recent devices have attempted to meet these challenges and give our opinion as to the necessary characteristics for the development of future devices.

Published
2020
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5. Effects of Flow Hydrodynamics and Eye Movements on Intraocular Drug Clearance

Author

Angeliki Velentza-Almpani, Nkiruka Ibeanu, Tianyang Liu, Christopher Redhead, Peng Tee Khaw, Steve Brocchini, Sahar Awwad, and Yann Bouremel

Subjects
ocular, pharmacokinetics, pharmaceutical modelling, convection, diffusion, saccades, Pharmacy and materia medica, RS1-441
Abstract

New in vitro prototypes (PK-Eye™) were tested with and without eye movement to understand diffusion and convection effects on intraocular clearance. Port placement in front ((i) ciliary inflow model) and behind the model lens ((ii) posterior inflow model) was used to study bevacizumab (1.25 mg/50 µL) and dexamethasone (0.1 mg/100 µL) in phosphate-buffered saline (PBS, pH 7.4) and simulated vitreal fluid (SVF). Dexamethasone was studied in a (iii) retinal-choroid-sclera (RCS) outflow model (with ciliary inflow and two outflow pathways). Ciliary vs. posterior inflow placement did not affect the half-life for dexamethasone at 2.0 µL/min using PBS (4.7 days vs. 4.8 days) and SVF (4.9 days with ciliary inflow), but it did decrease the half-life for bevacizumab in PBS (20.4 days vs. 2.4 days) and SVF (19.2 days vs. 10.8 days). Eye movement only affected the half-life of dexamethasone in both media. Dexamethasone in the RCS model showed approximately 20% and 75% clearance from the RCS and anterior outflows, respectively. The half-life of the protein was comparable to human data in the posterior inflow model. Shorter half-life values for a protein in a ciliary inflow model can be achieved with other eye movements. The RCS flow model with eye movement was comparable to human half-life data for dexamethasone.

Published
2022
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7. Novel approaches to model effects of subconjunctival blebs on flow pressure to improve clinical grading systems after glaucoma drainage surgery.

Author

Yann Bouremel, Richard M H Lee, Ian Eames, Steve Brocchini, and Peng Tee Khaw

Subjects
Medicine, Science
Abstract

Clinical grading systems following glaucoma filtration surgery do not include any effects of the bleb on the intra-ocular pressure and are relatively subjective, therefore carrying the risk of inter and/or intra-observer variability. The main objective of the study is to quantify and model the effect of subconjunctival bleb on flow pressure for assessment of clinical grading following glaucoma surgery. Subconjunctival bleb was created by inserting a tube into ex vivo rabbit eyes via an ab externo approach through the anterior chamber and exiting into the subconjunctival space. Sterile dyed water was injected through the tube into the developing bleb. For the in vitro approach a silicone bleb was created by clamping a circular silicone sheet, injecting dyed water through a fixed resistance outlet tube. Photographic measurements of the bleb height, planform area and pressure were taken as a function of time. Clinical blebs were also collected over a few months. Mathematical algorithm software was used to build the bleb model. Bleb height and volume increase as pressure in the bleb increases. The bleb planform area tended to a constant determined by the section of conjunctiva prior to shunt insertion. These increases were in accordance with the bleb model developed in the Appendix. They show that the pressure in the bleb is related to the resistance of the outflow. The linearity of clinical grading systems is reviewed and a new grading approach is proposed. The pressure in the bleb has a strong dependence on bleb extent, height and a weak dependence on conjunctival thickness. The pressure in a bleb can be estimated from bleb height, radius, and flow rate inlet in agreement with the bleb flow model. These results provide support for an improved bleb categorization system.

Published
2019
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8. Injectables and Depots to Prolong Drug Action of Proteins and Peptides

Author

Nkiruka Ibeanu, Raphael Egbu, Lesley Onyekuru, Hoda Javaheri, Peng Tee Khaw, Gareth R. Williams, Steve Brocchini, and Sahar Awwad

Subjects
half-life, drug delivery, ocular, subcutaneous, intravenous, oral, Pharmacy and materia medica, RS1-441
Abstract

Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological barriers, suboptimal biodistribution, and some proclivity for immunogenicity. Frequent administration of polypeptides is generally required to maintain adequate therapeutic levels, which can limit efficacy and compliance while increasing adverse reactions. Many strategies to increase the duration of action of therapeutic polypeptides have been described with many clinical products having been developed. This review describes approaches to optimise polypeptide delivery organised by the commonly used routes of administration. Future innovations in formulation may hold the key to the continued successful development of proteins and peptides with optimal clinical properties.

Published
2020
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9. Hydrodynamics of Intravitreal Injections into Liquid Vitreous Substitutes

Author

Christin Henein, Sahar Awwad, Nkiruka Ibeanu, Stavros Vlatakis, Steve Brocchini, Peng Tee Khaw, and Yann Bouremel

Subjects
hydrodynamics, hyaluronic acid, vitreous, intravitreal injection, distribution, viscosity, surface tension, density, Pharmacy and materia medica, RS1-441
Abstract

Intravitreal injections have become the cornerstone of retinal care and one of the most commonly performed procedures across all medical specialties. The impact of hydrodynamic forces of intravitreal solutions when injected into vitreous or vitreous substitutes has not been well described. While computational models do exist, they tend to underestimate the starting surface area of an injected bolus of a drug. Here, we report the dispersion profile of a dye bolus (50 µL) injected into different vitreous substitutes of varying viscosities, surface tensions, and volumetric densities. A novel 3D printed in vitro model of the vitreous cavity of the eye was designed to visualize the dispersion profile of solutions when injected into the following vitreous substitutes—balanced salt solution (BSS), sodium hyaluronate (HA), and silicone oils (SO)—using a 30G needle with a Reynolds number (Re) for injection ranging from approximately 189 to 677. Larger bolus surface areas were associated with faster injection speeds, lower viscosity of vitreous substitutes, and smaller difference in interfacial surface tensions. Boluses exhibited buoyancy when injected into standard S1000. The hydrodynamic properties of liquid vitreous substitutes influence the initial injected bolus dispersion profile and should be taken into account when simulating drug dispersion following intravitreal injection at a preclinical stage of development, to better inform formulations and performance.

Published
2019
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10. Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome.

Author

Morad Ansari, Jacqueline Rainger, Isabel M Hanson, Kathleen A Williamson, Freddie Sharkey, Louise Harewood, Angela Sandilands, Jill Clayton-Smith, Helene Dollfus, Pierre Bitoun, Francoise Meire, Judy Fantes, Brunella Franco, Birgit Lorenz, David S Taylor, Fiona Stewart, Colin E Willoughby, Meriel McEntagart, Peng Tee Khaw, Carol Clericuzio, Lionel Van Maldergem, Denise Williams, Ruth Newbury-Ecob, Elias I Traboulsi, Eduardo D Silva, Mukhlis M Madlom, David R Goudie, Brian W Fleck, Dagmar Wieczorek, Juergen Kohlhase, Alice D McTrusty, Carol Gardiner, Christopher Yale, Anthony T Moore, Isabelle Russell-Eggitt, Lily Islam, Melissa Lees, Philip L Beales, Stephen J Tuft, Juan B Solano, Miranda Splitt, Jens Michael Hertz, Trine E Prescott, Deborah J Shears, Ken K Nischal, Martine Doco-Fenzy, Fabienne Prieur, I Karen Temple, Katherine L Lachlan, Giuseppe Damante, Danny A Morrison, Veronica van Heyningen, and David R FitzPatrick

Subjects
Medicine, Science
Abstract

We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3' (telomeric) to PAX6 and one within a gene desert 5' (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia). Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome). Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated.

Published
2016
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12. A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Author

Rosie Clark, Samantha Sze-Yee Lee, Ran Du, Yining Wang, Sander C.M. Kneepkens, Jason Charng, Yu Huang, Michael L. Hunter, Chen Jiang, J.Willem L. Tideman, Ronald B. Melles, Caroline C.W. Klaver, David A. Mackey, Cathy Williams, Hélène Choquet, Kyoko Ohno-Matsui, Jeremy A. Guggenheim, Joan E. Bailey-Wilson, Paul N. Baird, Veluchamy A. Barathi, Ginevra Biino, Kathryn P. Burdon, Harry Campbell, Li Jia Chen, Ching-Yu Cheng, Emily Y. Chew, Jamie E. Craig, Margaret M. Deangelis, Cécile Delcourt, Xiaohu Ding, Qiao Fan, Maurizio Fossarello, Paul J. Foster, Puya Gharahkhani, Xiaobo Guo, Annechien E.G. Haarman, Toomas Haller, Christopher J. Hammond, Xikun Han, Caroline Hayward, Mingguang He, Alex W. Hewitt, Quan Hoang, Pirro G. Hysi, Adriana I. Iglesias, Robert P. Igo, Sudha K. Iyengar, Jost B. Jonas, Mika Kähönen, Jaakko Kaprio, Anthony P. Khawaja, Barbara E. Klein, Jonathan H. Lass, Kris Lee, Terho Lehtimäki, Deyana Lewis, Qing Li, Shi-Ming Li, Leo-Pekka Lyytikäinen, Stuart MacGregor, Nicholas G. Martin, Akira Meguro, Andres Metspalu, Candace Middlebrooks, Masahiro Miyake, Nobuhisa Mizuki, Anthony Musolf, Stefan Nickels, Konrad Oexle, Chi Pui Pang, Olavi Pärssinen, Andrew D. Paterson, Norbert Pfeiffer, Ozren Polasek, Jugnoo S. Rahi, Olli Raitakari, Igor Rudan, Srujana Sahebjada, Seang-Mei Saw, Claire L. Simpson, Dwight Stambolian, E-Shyong Tai, Milly S. Tedja, J. Willem L. Tideman, Akitaka Tsujikawa, Cornelia M. van Duijn, Virginie J.M. Verhoeven, Veronique Vitart, Ningli Wang, Ya Xing Wang, Juho Wedenoja, Wen Bin Wei, Katie M. Williams, James F. Wilson, Robert Wojciechowski, Jason C.S. Yam, Kenji Yamashiro, Maurice K.H. Yap, Seyhan Yazar, Shea Ping Yip, Terri L. Young, Xiangtian Zhou, Naomi Allen, Tariq Aslam, Denize Atan, Sarah Barman, Jenny Barrett, Paul Bishop, Graeme Black, Catey Bunce, Roxana Carare, Usha Chakravarthy, Michelle Chan, Sharon Chua, Valentina Cipriani, Alexander Day, Parul Desai, Bal Dhillon, Andrew Dick, Alexander Doney, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John Gallacher, David Garway-Heath, Jane Gibson, Dan Gore, Jeremy Guggenheim, Chris Hammond, Alison Hardcastle, Simon Harding, Ruth Hogg, Pirro Hysi, Pearse A. Keane, Peng Tee Khaw, Anthony Khawaja, Gerassimos Lascaratos, Thomas Littlejohns, Andrew Lotery, Phil Luthert, Tom MacGillivray, Sarah Mackie, Bernadette McGuinness, Gareth McKay, Martin McKibbin, Danny Mitry, Tony Moore, James Morgan, Zaynah Muthy, Eoin O'Sullivan, Chris Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Nikolas Pontikos, Jugnoo Rahi, Alicja Rudnicka, Jay Self, Panagiotis Sergouniotis, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Robyn Tapp, Caroline Thaung, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Stephen Vernon, Ananth Viswanathan, Katie Williams, Jayne Woodside, Max Yates, Jennifer Yip, Yalin Zheng, Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Epidemiology, Clinical Genetics, and Erasmus MC other

Subjects
All institutes and research themes of the Radboud University Medical Center, General Medicine, General Biochemistry, Genetics and Molecular Biology, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
Abstract

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).

Published
2023

13. The Association of Alcohol Consumption with Glaucoma and Related Traits

Author

Kelsey V. Stuart, Robert N. Luben, Alasdair N. Warwick, Kian M. Madjedi, Praveen J. Patel, Mahantesh I. Biradar, Zihan Sun, Mark A. Chia, Louis R. Pasquale, Janey L. Wiggs, Jae H. Kang, Jihye Kim, Hugues Aschard, Jessica H. Tran, Marleen A.H. Lentjes, Paul J. Foster, Anthony P. Khawaja, Mark Chia, Sharon Chua, Ron Do, Paul Foster, Jae Kang, Alan Kastner, Anthony Khawaja, Marleen Lentjes, Robert Luben, Kian Madjedi, Giovanni Montesano, Louis Pasquale, Kelsey Stuart, Alasdair Warwick, Janey Wiggs, Naomi Allen, Tariq Aslam, Denize Atan, Sarah Barman, Jenny Barrett, Paul Bishop, Graeme Black, Tasanee Braithwaite, Roxana Carare, Usha Chakravarthy, Michelle Chan, Alexander Day, Parul Desai, Bal Dhillon, Andrew Dick, Alexander Doney, Cathy Egan, Sarah Ennis, Marcus Fruttiger, John Gallacher, David (Ted) Garway-Heath, Jane Gibson, Jeremy Guggenheim, Chris Hammond, Alison Hardcastle, Simon Harding, Ruth Hogg, Pirro Hysi, Pearse Keane, Peng Tee Khaw, Gerassimos Lascaratos, Thomas Littlejohns, Andrew Lotery, Phil Luthert, Tom MacGillivray, Sarah Mackie, Bernadette McGuinness, Gareth McKay, Martin McKibbin, Tony Moore, James Morgan, Eoin O'Sullivan, Richard Oram, Chris Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Nikolas Pontikos, Jugnoo Rahi, Alicja Rudnicka, Naveed Sattar, Jay Self, Panagiotis Sergouniotis, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Robyn Tapp, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Ananth Viswanathan, Veronique Vitart, Mike Weedon, Katie Williams, Cathy Williams, Jayne Woodside, Max Yates, Jennifer Yip, Yalin Zheng, Tin Aung, Kathryn Burdon, Li Chen, Ching-Yu Cheng, Jamie Craig, Angela Cree, Victor de Vries, Sjoerd Driessen, John Fingert, Puya Gharahkhani, Christopher Hammond, Caroline Hayward, Alex Hewitt, Nomdo Jansonius, Fridbert Jonansson, Jost Jonas, Michael Kass, Chiea Khor, Caroline Klaver, Jacyline Koh, Stuart MacGregor, David Mackey, Paul Mitchell, Calvin Pang, Francesca Pasutto, Norbert Pfeiffer, Ozren Polašek, Wishal Ramdas, Alexander Schuster, Ayellet Segrè, Einer Stefansson, Kári Stefánsson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Cornelia van Duijn, Joëlle Vergroesen, Eranga Vithana, James Wilson, Robert Wojciechowski, Tien Wong, and Terri Young

Subjects
General Medicine
Published
2022

14. Development of an in vitro model to estimate mass transfer from the anterior cavity

Author

Tianyang Liu, Nkiruka Ibeanu, Steve Brocchini, Peng Tee Khaw, Yann Bouremel, and Sahar Awwad

Abstract

Knowledge of drug mass transfer from the anterior chamber via the iris-lens barrier has important implications for the development of front of the eye medicines that can also deliver drugs to the vitreous cavity. Here, the design and evaluation of a novel in vitro model that estimates anterior clearance (CL) kinetics is described. To mimic some aspects of the human eye to aid with pharmaceutical modelling, the model incorporated a simulation of aqueous inflow from the ciliary inlet at the physiological flow rate, two CL elimination pathways [anterior hyaloid pathway and retina choroid sclera (RCS) pathway], human cavity dimensions and use of simulated vitreous fluid (SVF). An eye movement platform that incorporated 3 different eye movements (smooth pursuit, microsaccadic and saccadic) was tested against the control (no movement) to observe any difference in anterior kinetics profile and drug convection to the posterior cavity. Both timolol and brimonidine injected in the intracameral space were evaluated in the new in vitro prototype. An initial release study with one selected eye movement (smooth pursuit) with timolol (6.8 ± 0.4 µg, 30 μL) and brimonidine (15.3 ± 1.5 µg, 30 μL) showed half-life values of 105.3 and 97.8 min respectively in the anterior cavity (AC) space. Another study evaluated the effect of all eye movements against control with both drugs with higher doses of timolol (146.0 ± 39.1 μg, 25 μL) and brimonidine (134.5 ± 39.5 μg, 25 μL). The amounts of timolol in the back of the eye (RCS membrane and outflow) were 0.07 ± 0.05%, 1.36 ± 0.88%, 1.55 ± 1.03% and 0.98 ± 0.06% by 8 h with smooth pursuit, microsaccadic, saccadic and no movement respectively; whereas brimonidine amounts were 0.70 ± 0.21%, 0.94 ± 0.40%, 1.48 ± 1.02%, and 0.76 ± 0.33% respectively. A small amount of both drugs was seen in other compartments in the model (lens part, iris part, hyaloid membrane part and silicone cornea). These results indicate that this model can be used to determine transfer of small molecules via the iris-lens barrier to help optimise front of the eye formulations to treat tissues further back in the eye.

Published
2022

15. Long-term Safety and Outcomes of β-radiation for Trabeculectomy

Author

Ian Murdoch, Renata Puertas, Mehran Hamedani, and Peng Tee Khaw

Subjects
Ophthalmology
Abstract

Beta-radiation is a neglected anti-scaring therapy with past concerns for safety. This report found it safe and efficacious when used as an adjuvant to trabeculectomy surgery in 101 people (135 eyes) over 20 years.Beta-radiation has been used as an adjunct to prevent scarring in trabeculectomy surgery for many decades. Safety concerns were raised with the use of high doses on bare sclera. Moorfields Eye Hospital has a large cohort of patients who have received beta-radiation therapy. We report a review of the long-term safety and efficacy.Cases undertaken between August 1992 and August 1996 were reviewed. Those with records available for postoperative review more than 5 years were included. Failure (reintervention/21 mmHg on 2 successive occasions) and any complication previously reported in association with β-radiation were the primary outcomes.In total, 292 operations using β-radiation were recorded and 101 people (135 eyes) with trabeculectomy surgery and post-operative follow-up for over 4.5 years were included. The median follow-up period was 22.5 years. At final follow-up 50 (48%) eyes had failed and 20/51 (51%) eyes with primary open angle glaucoma had had cataract surgery. Other complications were rare and associated with co-pathology.In glaucoma patients at risk of scarring and failure after trabeculectomy, as an anti-scarring adjuvant, a 750cGY dose of beta radiation was found to be safe and efficacious in the long-term.

Published
2022

17. International Study of Childhood Glaucoma

Author

Maria Papadopoulos, Elizabeth A. Vanner, Alana L. Grajewski, Arijit Mithra, Manju Pillai, Swati Upadhyaya, Ganesh Venkataraman, Ta Chen Peter Chang, Alana Grajewski, Elizabeth Hodapp, Velota Sung, Orna Geyer, Alvit Wolf, Ellen Mitchell, Ken Nischal, Sharon Freedman, Allen Beck, Annette Giangiacomo, Anne Coleman, Arif Khan, Anil Mandal, Sirisha Senthil, John Brookes, Peng Tee Khaw, Jocelyn Chua, Ching Lin Ho, James Brandt, Vera Essuman, Ray Areaux, Elena Bitrian, Franz Grehn, Thomas Klink, and Karen Joos

Subjects
Male, Intraocular pressure, Pediatrics, medicine.medical_specialty, Visual acuity, Adolescent, genetic structures, medicine.medical_treatment, Visual Acuity, MEDLINE, Glaucoma, Trabeculectomy, Global Health, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Prospective Studies, 0101 mathematics, Medical diagnosis, Child, Intraocular Pressure, business.industry, Incidence, 010102 general mathematics, General Medicine, Consecutive case series, Cataract surgery, medicine.disease, eye diseases, Clinical research, Child, Preschool, 030221 ophthalmology & optometry, Female, sense organs, medicine.symptom, business
Abstract

To ascertain the types of childhood glaucoma managed at major international centers, current clinical practice, and intraocular pressure (IOP) control and visual acuity (VA) outcomes.Prospective, multicenter, consecutive case series.All children with newly diagnosed glaucoma in at least 1 eye who fulfilled the Childhood Glaucoma Research Network (CGRN) definition of childhood glaucoma were recruited over a 1-year period with the aim of 18 months follow up.Demographic, clinical, management data (including complications), and outcomes (IOP and VA) were entered in a secure online database. All cases included in the outcome analysis had a minimum of 6 months follow-up.The management of childhood glaucoma, IOP control, and VA outcomes.A total of 441 children (691 eyes) with newly diagnosed glaucoma were enrolled from 17 international centers. Approximately 60% of patients came from 2 centers in India; however, 47.5% of Indian patients had no or less than 6 months of follow-up outcome data from diagnosis. Primary congenital glaucoma (PCG) was the most common diagnosis (45.4%, n = 314 eyes). There was a statistically significant association between diagnosis and ethnicity/race (P0.001), with PCG more frequent in nonwhite patients, glaucoma associated with acquired conditions more frequent in South Asian patients, and glaucoma after cataract surgery more frequent in white patients. The initial surgical procedure of choice for eyes with PCG significantly differed by country. Angle surgery alone was first line in centers in the United States, United Kingdom, Germany, Saudi Arabia, Singapore, and Israel (Group 1), whereas combined trabeculotomy-trabeculectomy was the first-line procedure for PCG in centers in India and Ghana (Group 2). There was no significant difference in IOP control nor VA between the 2 groups.The most common diagnoses in this international study of children with newly diagnosed glaucoma in order of frequency were PCG, glaucoma after congenital idiopathic cataract surgery, and glaucoma associated with trauma. Indian children had a disproportionately high loss to follow-up rate. Despite international differences in the surgical approach to PCG, there was no statistically significant difference in IOP or VA outcomes. We hope the results of this study will inform key areas of future international, collaborative clinical research in childhood glaucoma.

Published
2020

18. Feasibility of using patient-reported outcome measures with visually impaired children/young people attending paediatric ophthalmology clinics

Author

Val Tadic, Ameenat Solebo, Jugnoo Rahi, Sir Peng Tee Khaw, and Mario Cortina Borja

Subjects
Male, medicine.medical_specialty, Visual acuity, Outpatient Clinics, Hospital, Adolescent, genetic structures, Visually impaired, Visual impairment, education, Vision Disorders, Visual Acuity, BF, Prom, Pediatrics, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, London, medicine, Humans, 030212 general & internal medicine, Patient Reported Outcome Measures, Child, business.industry, Survival Analysis, Ophthalmology, Family medicine, Pediatrics, Perinatology and Child Health, 030221 ophthalmology & optometry, Quality of Life, Feasibility Studies, Pediatric ophthalmology, Patient-reported outcome, Female, medicine.symptom, business, Young person, Visually Impaired Persons, Qualitative research
Abstract

ObjectiveTo explore feasibility of using child/young person patient-reported outcome measures (PROMs) routinely in practice, using vision-specific instruments and paediatric ophthalmology as the exemplar.MethodsParticipants comprised patients aged 8–17 years, with visual impairment or low vision (visual acuity of the logarithm of the minimum angle of resolution (logMAR) worse than 0.3 in the better eye), attending the Department of Ophthalmology at Great Ormond Street Hospital, London, UK. All participants completed age-appropriate PROMs before attending their outpatient appointment. Half were randomly assigned to completion at home, with the choice of paper-and-pencil or electronic format. The other half were invited to complete PROMs during their hospital appointment, and randomly assigned to completion format. All participants completed a face-to-face survey exploring their attitudes and preferences. Analysis comprised survival analysis, and direct comparisons of proportions, with complementary qualitative data analysis.Results93 patients participated. 48 (98%) completing PROMs at home chose the paper-and-pencil format. Completion at home took longer than at hospital (median=20, vs 14 min, pConclusionPROM completion at home ahead of hospital appointments may be preferable for collecting complete, high-quality datasets. Despite equipoise on preference for format, the majority of those completing at home chose the traditional paper-and-pencil format, despite impaired sight. These findings should inform implementation of child/young person PROMs into routine practice.

Published
2021

21. An Age- and Stage-Appropriate Patient-Reported Outcome Measure of Vision-Related Quality of Life of Children and Young People with Visual Impairment

Author

Val Tadic, Ameenat Solebo, Jugnoo Rahi, Alki Liasis, Sir Peng Tee Khaw, and Mario Cortina Borja

Subjects
Male, Activities of daily living, Biometry, Adolescent, Psychometrics, Visual impairment, Vision Disorders, Visual Acuity, Validity, 03 medical and health sciences, Disability Evaluation, Young Adult, 0302 clinical medicine, Quality of life (healthcare), Sickness Impact Profile, Surveys and Questionnaires, Activities of Daily Living, medicine, Humans, Patient Reported Outcome Measures, Child, Vision, Ocular, 030304 developmental biology, 0303 health sciences, Rasch model, business.industry, Construct validity, Differential item functioning, Ophthalmology, 030221 ophthalmology & optometry, Quality of Life, Patient-reported outcome, Female, medicine.symptom, business, Visually Impaired Persons, Clinical psychology
Abstract

Purpose Developmentally sensitive measures of vision-related quality of life (VQoL) are needed to capture age-specific concerns about the impact of living with visual impairment (VI) in children and young people. Our objective was to use our validated VQoL instrument for children and young people 10 to 15 years of age (the VQoL_CYP) as the foundation for development of age-specific extensions. Design Questionnaire development. Participants A representative sample of children and young people 6 to 19 years of age with VI, defined as visual acuity worse than 0.50 logarithm of the minimum angle of resolution in the better eye. They were recruited from pediatric ophthalmology clinics at Great Ormond Street Hospital and Moorfields Eye Hospital and, in the final phase of the study, from 20 additional United Kingdom hospitals. Methods Standard instrument development processes were followed across 4 phases. Twenty-nine semistructured interviews with children and young people permitted draft age-appropriate extensions. Twenty-eight cognitive interviews informed items and response options. Age-appropriate extensions were prepiloted with 49 participants to ensure feasibility and administered via a postal survey to a national sample of 160 participants for psychometric evaluation using Rasch analysis. Construct validity was evaluated through correlations with the Pediatric Quality of Life Inventory. Main Outcome Measures Psychometric indices of validity and reliability of the instrument versions. Results Interviews confirmed that the existing VQoL_CYP content and format were relevant across a wider age range. Age-appropriate extensions were drafted for children (8–12 years) and young people (13–17 years). Psychometric item reduction produced 20-item child and 22-item young person versions, each with acceptable fit values, no notable differential item functioning, good measurement precision, ordered response categories and acceptable targeting, and no notable differential item functioning on items common to both. Construct validity was demonstrated through correlations with health-related quality of life (r = 0.698). Conclusions Using an efficient child- and young person–centered approach, we developed 2 robust, age-appropriate versions of an instrument capturing VQoL that can be used cross-sectionally or sequentially across the age range of 8 to 17 years in research and clinical practice. This approach may be applicable in other rare childhood ophthalmic disorders.

Published
2018

22. Spectral-Domain Optical Coherence Tomography Imaging in 67 321 Adults

Author

Andrew Lotery, David Garway-Heath, Pearse Keane, Jugnoo Rahi, Carlota Grossi, Paul Foster, Anthony Khawaja, Cathie Sudlow, Tariq Aslam, Sir Peng Tee Khaw, Tunde Peto, Christopher Hammond, Max Yates, and John Gallacher

Subjects
Refractive error, medicine.medical_specialty, Visual acuity, genetic structures, medicine.diagnostic_test, Cross-sectional study, business.industry, Diabetic retinopathy, medicine.disease, eye diseases, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Optical coherence tomography, 030221 ophthalmology & optometry, medicine, Optometry, sense organs, medicine.symptom, Prospective cohort study, business, 030217 neurology & neurosurgery, Dioptre, Cohort study
Abstract

Purpose To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biobank (UKBB) study. Design Large, multisite cohort study in the United Kingdom. Analysis of cross-sectional data. Participants Adults from the United Kingdom aged 40 to 69 years. Methods Participants had nonmydriatic SD OCT (Topcon 3D OCT-1000 Mark II; Topcon GB, Newberry, Berkshire, UK) performed as part of the ocular assessment module. Rapid, remote, automated segmentation of the images was performed using custom optical coherence tomography (OCT) image analysis software (Topcon Advanced Boundary Segmentation [TABS]; Topcon GB) to generate macular thickness values. We excluded people with a history of ocular or systemic disease (diabetes or neurodegenerative diseases) and eyes with reduced vision ( Main Outcome Measures Macular thickness values across 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields. Results The SD OCT scans of 67 321 subjects were available for analysis, with 32 062 people with at least 1 eye meeting the inclusion criteria. There were 17 274 women and 14 788 men, with a mean (standard deviation [SD]) age of 55.2 (8.2) years. The mean (SD) logarithm of the minimum angle of resolution visual acuity was −0.075 (0.087), and the refractive error was −0.071 (+1.91) diopters (D). The mean (SD) central macular thickness (CMT) in the central 1-mm ETDRS subfield was 264.5 (22.9) μm, with 95% confidence limits of 220.8 and 311.5 μm. After adjusting for covariates, CMT was positively correlated with older age, female gender, greater myopia, smoking, body mass index (BMI), and white ethnicity (all P Conclusions We report macular thickness data derived from SD OCT images collected as part of the UKBB study and found novel associations among older age, ethnicity, BMI, smoking, and macular thickness.

Published
2016

25. Automated quantification of retinal vessel morphometry in the UK biobank cohort

Author

Christopher Owen, Andrew Lotery, Ruth Hogg, Pearse Keane, Jugnoo Rahi, Catey Bunce, Paul Foster, Anthony Khawaja, Bernadette McGuinness, David Steel, Tariq Aslam, Sir Peng Tee Khaw, Gareth McKay, Cathy Williams, Alicja R Rudnicka, Katie M Williams, Irene Stratton, Adnan Tufail, Andrew Dick, and Max Yates

Subjects
Ground truth, business.industry, Retinal, Image segmentation, Biobank, Retinal image, 030218 nuclear medicine & medical imaging, Retinal vessel, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Cohort, Medical imaging, Medicine, 030212 general & internal medicine, business, Cartography
Abstract

The morphometric characteristics of the retinal vascular network have been associated with risk markers of many systemic and vascular diseases. However, analysis of data from large population based studies is needed to help resolve uncertainties in these associations. QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) is a fully automated retinal image analysis system that has been designed to process large numbers of retinal images and obtains quantitative measures of vessel morphology to be used in epidemiological studies. QUARTZ has been used to process retinal images from UK Biobank which is a large population-based cohort study. In this paper, we address issues of robustness with respect to processing large datasets and validate QUARTZ using a subset of 4,692 UK Biobank retinal images. Ground truth data produced by human observers for validation have been made available online. Following validation, 135,867 retinal images (68,549 participants) from the UK Biobank study were processed by QUARTZ. 71.53% of these images were classified as being of adequate quality, which equated to 80.90% participants with at least one image of adequate quality. The vessel morphometric data are currently being used in epidemiological studies. The intention of the UK Biobank Eye and Vision Consortium is to include these derived measures in the UK Biobank data archive.

Published
2017

26. Visual field progression 8 years after trabeculectomy in Asian eyes: results from The Singapore 5-Fluorouracil Study.

Author

Ang, Bryan C. H., Seen, Sophia, Kumaran, Arjunan, Sim De Leon, John Mark, Kah Leng Seah, Steve, Foster, Paul J., Gazzard, Gus, Htoon, Hla M., Peng Tee Khaw, Tin Aung, and Husain, Rahat

Abstract

Background/Aims This work aimed to study the effect of long-term intraocular pressure (IOP) fluctuation on visual field (VF) progression 8 years post-trabeculectomy in Asian eyes. Methods This was a retrospective analysis of 8-year post-trabeculectomy data from The Singapore 5-Fluorouracil (5-FU) Study. VFs were analysed using Progressor software (Medisoft, Leeds, UK). Outcome measures included mean slope for VF per year, number of progressing points and mean slope for progressing points per year. Multivariate regression analyses were performed adjusting for age, gender, ethnicity, glaucoma type, intraoperative 5-FU, diabetes mellitus, hypertension, best pre-trabeculectomy VF mean deviation, post-trabeculectomy mean IOP, IOP reduction and IOP fluctuation (SD of IOPs at 6-monthly timepoints). Results 127 (52.3%) subjects completed 8-year follow-up with ≥5 reliable VFs and =8 6-monthly IOP measurements. Mean age was 61.8±9.6 years. Post-operatively, mean IOP was 14.2±2.8 mm Hg and mean IOP fluctuation was 2.53±1.20 mm Hg. Higher IOP fluctuation was associated with greater mean slope for field (B=-0.071; p=0.013), number of progressing points (B=0.963; p=0.014) and VF progression as defined by ≥1 progressing point (OR=1.585; p=0.029). There was also a trend towards eyes with higher IOP fluctuation having ≥3 adjacent progressing points in the same hemifield (OR=1.489; p=0.055). Greater mean IOP reduction post-trabeculectomy was associated only with a lower mean slope for progressing points per year (B=-0.026; p=0.028). There was no significant effect of intra-operative 5-FU compared with placebo for all outcome measures. Conclusion In post-trabeculectomy Asian eyes with well-controlled IOP, higher long-term IOP fluctuation may be associated with greater VF progression. [ABSTRACT FROM AUTHOR]

Published
2020
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27. Enhanced Trabeculectomy: The Moorfields Safer Surgery System

Author

Peng Tee, Khaw, Mark, Chiang, Peter, Shah, Freda, Sii, Alastair, Lockwood, and Ashkan, Khalili

Subjects
Postoperative Complications, Treatment Outcome, Trabecular Meshwork, Suture Techniques, Humans, Glaucoma, Trabeculectomy, Surgical Flaps, Intraocular Pressure, Sclera
Abstract

Trabeculectomy with antifibrotic treatment is still the most popular incisional procedure for glaucoma filtration surgery (GFS) worldwide. The advent of antifibrotic agents reduced failure due to scarring but resulted in increased complications. Advances in trabeculectomy surgery have been driven by the need to minimise the risk of: (1) complications and (2) surgical failure. This chapter covers preoperative, intraoperative, and postoperative strategies, which improve the outcome of GFS. Strategies to reduce the risk of complications centre on the prevention of postoperative hypotony by minimising the risk of overdrainage, postoperative wound leaks, and poor bleb morphology. Surgical techniques to reduce the risk of postoperative fibrosis by the use of antifibrotic agents (including mitomycin C) are discussed in detail. These techniques are based on a combination of considerable clinical experience, observation, and laboratory research. The need to address pre-, intra-, and postoperative issues in each individual patient is emphasised. These changes are embodied in the system we call the "Moorfields Safer Surgery System." The use of these strategies has considerably reduced the incidence of major complications, including hypotony, cystic blebs, and endophthalmitis in practices around the world. Most of these techniques are simple, require minimal equipment, and can be easily mastered. They are associated with an improvement in overall outcome and it is hoped that this chapter will help the reader benefit from these advances.

Published
2017

29. Preliminaries

Author

Paolo Bettin and Sir Peng Tee Khaw

Published
2017

30. List of Contributors

Author

Luis Amaya, Jane L Ashworth, Robert A Avery, Jack Bartram, Shannon J Beres, Gil Binenbaum, Valérie Biousse, Eileen E Birch, Susmito Biswas, Graeme C M Black, Joanna Black, Richard J C Bowman, John A Bradbury, Michael C Brodsky, Donal Brosnahan, Alejandra de Alba, Jayne E Camuglia, Susan M Carden, Giovanni Castano, Ingele Casteels, Yvonne Chung, Michael P Clarke, David K Coats, Richard Collin, John Crompton, Emmett T Cunningham, Joseph L Demer, Hélène Dollfus, Peter J Dolman, Sean P Donahue, Clive Edelsten, Alistair R Fielder, David R. FitzPatrick, Anne B Fulton, Brenda L Gallie, Megan Geloneck, Clare E Gilbert, Christy Giligson, Glen A Gole, William V Good, John R B Grigg, Hans Grossniklaus, Patrick Hamel, Sheryl M Handler, Ronald M Hansen, Gena Heidary, Richard W Hertle, Göran Darius Hildebrand, Graham E Holder, Creig S Hoyt, G Baker Hubbard, Amy K Hutchinson, Saurabh Jain, Robyn V Jamieson, Hanne Jensen, Nadja Kadom, Ramesh Kekunnaya, Robert C Kersten, Philippe Kestelyn, Jan E E Keunen, Peng Tee Khaw, Chong Ae Kim, Jan Koopman, Stephen P Kraft, Burton J Kushner, Scott R Lambert, G Robert LaRoche, Dorte Ancher Larsen, Andrew G Lee, Barry Lee, Phoebe Lenhart, Alki Liasis, Grant T Liu, Christopher Lloyd, Christopher J Lyons, Carey A Matsuba, Caroline J MacEwen, Alan A McNab, Vaishali Mehta, Michel Michaelides, Daniel Mojon, Hans Ulrik, Anthony T Moore, Andrew A M Morris, Nancy J Newman, Ken K Nischal, Una O'Colmain, Anna R O'Connor, Michael O'Keefe, Scott E Olitsky, Luis H Ospina, Darren T Oystreck, Maria Papadopoulos, Sunju Park, Evelyn A Paysse, Jason H Peragallo, Erika Mota Pereira, Rachel F Pilling, Stacy Pineles, Venkatesh Prajna, Frank Antony Proudlock, Narman Puvanachandra, Anthony G Quinn, Graham E Quinn, Jugnoo S Rahi, Michael X Repka, Joshua Robinson, Buddy Russell, Luis Carlos Ferreira de Sá, Virender Sachdeva, Daniel J Salchow, Richard L Scawn, Nicoline Schalij-Delfos, Mary J van Schooneveld, Jay Self, Panagiotis I Sergouniotis, Carol L Shields, Jerry A Shields, John J Sloper, Martin P Snead, Sameh E Soliman, Timothy John Sullivan, C Gail Summers, Kimberley Tan, David S Taylor, Dorothy A Thompson, Elias I Traboulsi, Stephen J Tuft, Jimmy M Uddin, Perumalsamy Vijayalakshmi, Patrick Watts, David R Weakley, and Jill Razor Wells

Published
2017

31. Central corneal thickness in glaucoma

Author

Chelvin Sng, Keith Barton, Gus Gazzard, and Sir Peng Tee Khaw

Subjects
0301 basic medicine, medicine.medical_specialty, genetic structures, Corneal Pachymetry, Ocular hypertension, Glaucoma, Context (language use), Cornea thickness, Cornea, 03 medical and health sciences, Tonometry, Ocular, 0302 clinical medicine, Ophthalmology, medicine, Humans, Clinical significance, In patient, Corneal pachymetry, Intraocular Pressure, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, eye diseases, 030104 developmental biology, medicine.anatomical_structure, 030221 ophthalmology & optometry, Ocular Hypertension, sense organs, business
Abstract

Purpose of review The purpose of this review is to summarize the role of central corneal thickness (CCT) in the clinical management of a glaucoma patient. Recent findings The prognostic value of CCT is well recognized in patients with ocular hypertension. However, its predictive value in other glaucoma suspects and patients with established glaucoma is less certain. Tonometry artefacts can result from variations in CCT. However, an adequately validated correction algorithm for Goldmann applanation tonometry measurements does not exist. Newer methods of tonometry are potentially less influenced by CCT but are limited in their clinical use. There may also be biological and genetic associations between corneal thickness and glaucoma. Demographics, environmental factors, glaucoma treatment and the measurement device used have a significant influence on CCT, and should be considered when interpreting the effect of cornea thickness in patients with glaucoma. New measurements of the biomechanical properties of the cornea are likely to be better approximations of the globe biomechanics than CCT, but these require further evaluation. Summary The clinical significance of CCT is well recognized in the context of glaucoma diagnosis and management, though the extent of its importance remains debatable. Corneal biomechanical properties may be more significantly associated with glaucoma than CCT.

Published
2016

32. Glaucoma

Author

Andrew Tatham and Peng Tee Khaw

Subjects
genetic structures, sense organs, eye diseases
Abstract

This chapter explores glaucoma. It starts off with an outline of optic nerve head anatomy and then describes aqueous fluid dynamics and the pathogenesis of glaucoma. It then goes on to discuss the clinical skill areas of optic nerve head assessment in glaucoma, glaucoma imaging devices, tonometry and tachymetry, gonioscopy, and perimetry. The chapter also details ocular hypertension, primary open-angle glaucoma, primary angle closure, and secondary angle closure. In addition, it discusses normal tension glaucoma, steroid-induced glaucoma, traumatic glaucoma, inflammatory glaucomas, pseudoexfoliative glaucoma, pigmentary glaucoma, and neovascular glaucoma. It then covers aqueous misdirection, iridocorneal endothelial syndrome and iridocorneal dysgenesis, ocular hypotensive agents, laser therapy for glaucoma, and glaucoma surgery.

Published
2016

33. Training in Ophthalmology

Author

Venki Sundaram, Allon Barsam, Lucy Barker, Peng Tee Khaw, Venki Sundaram, Allon Barsam, Lucy Barker, and Peng Tee Khaw

Subjects
Eye--Diseases, Ophthalmology, Ophthalmology--Examinations--Study guides
Abstract

The second edition of this excellent and highly popular textbook continues to address the Royal College of Ophthalmologists (RCOphth) syllabus for trainee ophthalmologists and is an essential read for those studying ophthalmology, optometry and orthoptics. As a theoretical and practical aid, it guides readers through postgraduate Ophthalmic Specialist Training. Emphasis is placed on the practical assessment and management of key ophthalmic conditions. Clearly laid out and highly illustrated in full colour throughout, each condition is discussed in two or three-pages, beginning with general explanations of the pathophysiology and clinical evaluation, followed by differential diagnoses and treatment options. This thoroughly revised second edition includes new chapters on paediatric ophthalmology, refractive surgery and microsurgical skills. This text will appeal to foundation doctors, specialist trainees in ophthalmology, candidates preparing for the Fellowship of the Royal College of Ophthalmology (FRCOphth) examination, consultants in ophthalmology and practitioners looking for a comprehensive but accessible guide to the subject.

Published
2016

34. Geographical variation in glaucoma prescribing trends in England 2008-2012: an observational ecological study

Author

Jacob S, Heng, Richard, Wormald, and Peng Tee, Khaw

Subjects
Adult, Male, genetic structures, Drug Prescriptions, Ethnicity, Humans, EPIDEMIOLOGY, Practice Patterns, Physicians', Sex Distribution, Antihypertensive Agents, Aged, Demography, Research, Middle Aged, eye diseases, Ophthalmology, England, Female, Ocular Hypertension, sense organs, Visual Fields, Glaucoma, Open-Angle
Abstract

Objectives To explore (1) the national trend in population-adjusted prescription rates for glaucoma and ocular hypertension (OHT) in England and (2) any geographical variation in glaucoma/OHT prescribing trends and its association with established risk factors for primary open-angle glaucoma (POAG) at the population level. Design Observational ecological study. Setting Primary care in England 2008–2012. Participants All patients who received 1 or more of the 37 778 660 glaucoma/OHT prescription items between 2008 and 2012. Primary and secondary outcome measure methods Glaucoma/OHT prescription statistics for England and its constituent primary care trusts (PCTs) between 2008 and 2012 were divided by annual population estimates to give prescription rates per 100 000 population aged ≥40 years. To examine regional differences, prescription rates and the change in prescription rates between 2008 and 2012 for PCTs were separately entered into multivariable linear regression models with the population proportion aged ≥60 years; the proportion of males; the proportion of West African Diaspora (WAD) ethnicity; PCT funding per capita; Index of Multiple Deprivation 2010 score and its domains. Results Between 2008 and 2012, glaucoma/OHT prescriptions increased from 28 029 to 31 309 items per 100 000 population aged ≥40 years. Between PCTs, nearly a quarter of the variation in prescription rates in 2008 and 2012 could be attributed to age, WAD ethnicity and male gender. The change in prescription rates between 2008 and 2012 was only modestly correlated with age (p=0.003, β=0.234), and income deprivation (p=0.035, β=−0.168). Conclusions Increased population-adjusted glaucoma/OHT prescription rates in the study period were likely due to increased detection of POAG and OHT cases at risk of POAG. Between PCTs, regional variation in overall prescription rates was partly attributable to demographic risk factors for POAG, although the change in prescription rates was only modestly correlated with the same risk factors, suggesting potential variation in practice.

Published
2016

35. Ophthalmology

Author

Helen Gibbons and Sir Peng Tee Khaw

Subjects
genetic structures, sense organs, eye diseases
Abstract

Ophthalmology nursing is highly specialized, and this chapter highlights the anatomy of the eye and the process for assessing patients with visual problems and common clinical conditions of the eye. These conditions include glaucoma, cataracts, trauma and injuries of the eye, and benign conditions. This chapter highlights the presenting features of the condition, assessment, treatment, and care needs for the surgical nurse.

Published
2016

37. Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies

Author

Christopher Owen, Sarah Barman, Philip Luthert, Ruth Hogg, Pearse Keane, Jugnoo Rahi, Catey Bunce, Carlota Grossi, Paul Foster, Anthony Khawaja, Bernadette McGuinness, David Steel, Tariq Aslam, Emanuele Trucco, Sir Peng Tee Khaw, Gareth McKay, Peter Whincup, Alicja R Rudnicka, Alexander C Day, Muhammad Moazam Fraz, Katie M Williams, Irene Stratton, Usha Chakravarthy, Adnan Tufail, Andrew Dick, and Max Yates

Subjects
Adult, Male, Image quality, Datasets as Topic, Health Informatics, 02 engineering and technology, computer.software_genre, Retina, chemistry.chemical_compound, Random Allocation, Software, 0202 electrical engineering, electronic engineering, information engineering, Medicine, Humans, Vascular Diseases, Aged, business.industry, Retinal Vessels, 020207 software engineering, Retinal, Middle Aged, Image Enhancement, Automation, Biobank, United Kingdom, Computer Science Applications, medicine.anatomical_structure, chemistry, Data analysis, 020201 artificial intelligence & image processing, Female, Data mining, business, computer, Algorithms
Abstract

Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost. Changes in retinal vasculature prospectively associated with disease outcomes.Large population based studies help to resolve uncertainties in these associations.QUARTZ software extracts morphometric data from large numbers of retinal images.Automated image quality assessment is required to achieve full automation.This addition into QUARTZ makes processing the entire UK Biobank dataset feasible.

Published
2015

38. Role of Educational Exposure in the Association Between Myopia and Birth Order

Author

Jeremy Guggenheim, David Garway-Heath, Jugnoo Rahi, Catey Bunce, Cathie Sudlow, Tariq Aslam, Sir Peng Tee Khaw, Cathy Williams, Christopher Hammond, Max Yates, and John Gallacher

Subjects
Adult, Male, medicine.medical_specialty, genetic structures, Cross-sectional study, Population, Logistic regression, Article, Risk Factors, Surveys and Questionnaires, Epidemiology, medicine, Myopia, Odds Ratio, Prevalence, Humans, education, Dioptre, Aged, education.field_of_study, business.industry, Odds ratio, Middle Aged, eye diseases, United Kingdom, Ophthalmology, Birth order, Cross-Sectional Studies, Optometry, Eye disorder, Educational Status, Female, Birth Order, business, Demography
Abstract

Importance Visual impairment due to myopia is an important public health issue. A prior analysis of population-based cohorts aged 15 to 22 years recruited from the United Kingdom and Israel suggested myopia and high myopia were approximately 10% more common in first-born compared with later-born children. Objective To examine whether myopia was associated with birth order in an earlier generation than studied previously and, if so, whether the association was attenuated after adjusting for education exposure, as predicted by the hypothesis that the education of children with later birth orders is less intense. Design, Setting, and Participants Cross-sectional study of UK Biobank participants recruited from 2006 to 2010. Analysis was restricted to participants aged 40 to 69 years who had a vision assessment, self-reported white ethnicity, and no history of eye disorders (N = 89 120). Myopia and high myopia were defined as autorefraction of −0.75 diopters (D) or less and −6.00 D or less, respectively. Exposures Birth order and information on potential confounders including highest educational qualification ascertained using a structured questionnaire. Main Outcomes and Measures Odds ratios (ORs) for myopia and high myopia by birth order, using logistic regression and adjusting for age and sex (model 1) or age, sex, and highest educational qualification (model 2). Results In model 1 (no adjustment for education), birth order was associated with both myopia and high myopia (eg, comparing first- vs second-born individuals; OR, 1.12; 95% CI, 1.08-1.16; P = 1.40E-11 and OR, 1.21; 95% CI, 1.11-1.30; P = 3.60E-06 for myopia and high myopia, respectively). The risk for myopia became progressively lower for later birth orders, suggesting a dose response. In model 2 (after adjusting for education), the effect sizes were attenuated by approximately 25% (OR, 1.09; 95% CI, 1.05-1.12; P = 1.30E-06 and OR, 1.15; 95% CI, 1.06-1.25; P = 4.60E-04 for myopia and high myopia, respectively) and the apparent dose response was abolished. Conclusions and Relevance These data suggest that the association between birth order and myopia is not due to a new environmental pressure in the last 30 to 40 years. The attenuated effect size after adjusting for educational exposure supports a role for reduced parental investment in education of children with later birth orders in their relative protection from myopia.

Published
2015

39. Erratum

Author

Maryse Bailly and Sir Peng Tee Khaw

Subjects
Erratum
Published
2018

40. List of Contributors

Author

Leslie Abrams-Tobe, Samer A Abuswider, Jorge Acosta, Pavi Agrawal, Oscar Albis-Donado, Luciana M Alencar, R Rand Allingham, Annahita Amireskandari, Nitin Anand, Florent Aptel, Makoto Araie, Enyr S Arcieri, Ehud I Assia, Tin Aung, George Baerveldt, Nafees Baig, Annie K Baik, Rajendra K Bansal, Mirko Babic, Anita Barikian, Howard Barnebey, Keith Barton, Christophe Baudouin, Allen Beck, Sonya L Bennett, Stanley J Berke, Tui H Bevin, Shibal Bhartiya, Philip A Bloom, Dana M Blumberg, Kathryn Bollinger, Christopher Bowd, John W Boyle, James D Brandt, David C Broadway, Stephen Brocchini, Alain M Bron, Donald L Budenz, Catey Bunce, Claude F Burgoyne, Jennifer Burr, Yvonne M Buys, Louis B Cantor, Joseph Caprioli, Roberto G Carassa, Daniel S Casper, Yara Paula Catoira-Boyle, Piero Ceruti, Debasis Chakrabarti, Raka Chakrabarti, Pratap Challa, Errol Chan, Peter T Chang, Robert T Chang, Balwantray C Chauhan, Aiyin Chen, Jason Cheng, Paul TK Chew, Mark Chiang, Etsuo Chihara, Neil T Choplin, George A Cioffi, Colin I Clement, Anne L Coleman, Nathan G Congdon, Michael A Coote, Vital P Costa, David P Crabb, Alan S Crandall, E Randy Craven, Laura Crawley, Jonathan G Crowston, Emmett T Cunningham, Elie Dahan, Annegret H Dahlmann-Noor, Karim F Damji, Alexander Day, Me'Ja Day, Philippe Denis, Syril Dorairaj, J Crawford Downs, Gordon N Dutton, Hassan Eldaly, Fathi F El Sayyad, Benedetto Falsini, Francisco Fantes, Herbert P Fechter, Robert D Fechtner, Ronald L Fellman, Eva Fenwick, Arosha Fernando, Ann Caroline Fisher, Frederick W Fitzke, Brad Fortune, Paul Foster, Panayiota Founti, Jeffrey Freedman, Stefano A Gandolfi, Julián García-Feijoó, David Garway-Heath, Gus Gazzard, Steven J Gedde, Noa Geffen, Stelios Georgoulas, Annette Giangiacomo, Katie Gill, Zisis Gkatzioufas, Ivan Goldberg, Pieter Gouws, Stuart L Graham, Alana L Grajewski, David S Greenfield, Franz Grehn, Daniel E Grigera, Ronald L Gross, Davinder S Grover, Rafael Grytz, Meenakashi Gupta, Neeru Gupta, Carlos Gustavo de Moraes, Ali S Hafez, Farhad Hafezi, Teruhiko Hamanaka, Alon Harris, Marcelo Hatanaka, Matthew J Hawker, Paul R Healey, The late Catherine J Heatley, Dale K Heuer, Eve J Higginbotham, Cornelia Hirn, Roger A Hitchings, Gábor Holló, Ann M Hoste, Andrew Huck, Cindy ML Hutnik, Camille Hylton, Sabita M Ittoop, Farrah Ja'afar, Henry Jampel, Thomas V Johnson, Jost B Jonas, Malik Y Kahook, Michael A Kass, Andreas Katsanos, L Jay Katz, Jill E Keeffe, Thomas Kersey, Naira Khachatryan, Sir Peng Tee Khaw, Albert S Khouri, Dan Kiage, Lee Kiang, Danny Kim, Yoshiaki Kiuchi, Thomas Klink, Helen Koenigsman, Anastasios GP Konstas, Aachal Kotecha, Avinash Kulkarni, Alexander V Kuroyedov, Antoine Labbé, Alan Lacey, Dennis SC Lam, Ecosse L Lamourex, Graham Lee, Paul Lee, Hans G Lemij, Anthony Leoncavallo, Mark R Lesk, Christopher KS Leung, Dexter YL Leung, Leonard A Levin, Richard A Lewis, K Sheng Lim, Ridia Lim, Ricardo de Lima, Yutao Liu, Alastair Lockwood, Sancy Low, Fumihiko Mabuchi, David A Mackey, Rizwan Malik, Anil K Mandal, Steven L Mansberger, Kaweh Mansouri, Giorgio Marchini, Manjula Marella, Keith R Martin, Robert H McGlynn, Steven H McKinley, Stuart J McKinnon, J Ryan McManus, Felipe A Medeiros, André Mermoud, Clive S Migdal, Don Minckler, Anthony CB Molteno, Paolo Mora, Javier Moreno-Montañés, James E Morgan, Sameh Mosaed, Marilita M Moschos, Kelly W Muir, Gonzalo Muñoz, Francisco J Muñoz-Negrete, Arvind Neelakantan, Anil K Negi, Peter A Netland, Paula Anne Newman-Casey, Marcelo T Nicolela, Nuwan Niyadurupola, Magdy A Nofal, Winnie Nolan, Monisha E Nongpiur, Baha'a N Noureddin, Gary D Novack, Brenda Nuyen, Krishnamurthy Palaniswamy, Camille Palma, Ki Ho Park, Richard K Parrish, Maria Papadopoulos, Rajul S Parikh, Louis R Pasquale, Alice Pébay, Sergey Petrov, Jody Piltz-Seymour, Luís Abegão Pinto, Ian F Pitha, Norbert Pfeiffer, Luciano Quaranta, Pradeep Y Ramulu, Emilie Ravinet, Tony Realini, Gema Rebolleda, Nic J Reus, Adam C Reynolds, Douglas J Rhee, Isabelle Riss, Robert Ritch, Charles E Riva, Gloria Roberti, Cynthia J Roberts, Alan L Robin, Prin Rojanapongpun, Sylvain Roy, John F Salmon, Juan Roberto Sampaolesi, Chiara Sangermani, Usman A Sarodia, Jamie Lea Schaefer, Ursula Schloetzer-Schrehardt, Gregory S Schultz, Joel S Schuman, Leonard K Seibold, Tarek M Shaarawy, Peter Shah, Mark B Sherwood, Lineu Oto Shiroma, Brent Siesky, Sergio Estrela Silva, Annapurna Singh, Arun D Singh, Kuldev Singh, Chelvin CA Sng, Brian J Song, George L Spaeth, Alexander Spratt, Ingeborg Stalmans, Robert L Stamper, Kazuhisa Sugiyama, Remo Susanna, Orathai Suwanpimolkul, William H Swanson, Ernst R Tamm, Tak Yee Tania Tai, Angelo P Tanna, Chaiwat Teekhasaenee, Clement CY Tham, Hagen Thieme, Ravi Thomas, Andrew M Thompson, Ravilla D Thulasiraj, John Thygesen, Karim Tomey, Yokrat Ton, Fotis Topouzis, Carol B Toris, Roberto Tosi, James C Tsai, Sonal S Tuli, Anja Tuulonen, Nicola Ungaro, Luke Vale, Leonieke ME van Koolwijk, Reena S Vaswani, Rengaraj Venkatesh, Cristina Venturini, Stephen A Vernon, Eranga N Vithana, Lingam Vijaya, Ananth C Viswanathan, Gabriele Vizzari, Irini C Voudouragkaki, Michael Waisbourd, Mark J Walland, Robert N Weinreb, Mark Werner, Anthony Wells, Boateng Wiafe, Jacob Wilensky, Tina T Wong, Darrell WuDunn, Jennifer LY Yip, Yeni Yucel, Linda M Zangwill, Virginia E Zanutigh, Joseph R Zelefsky, and Thierry Zeyen

Published
2015

41. Goniotomy and Trabeculotomy

Author

Sir Peng Tee Khaw and Maria Papadopoulos

Subjects
medicine.medical_specialty, business.industry, Ophthalmology, medicine, business, Trabeculotomy
Published
2015

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

Author

Sharon Yu Lin Chua, Thomas, Dhanes, Allen, Naomi, Lotery, Andrew, Desai, Parul, Patel, Praveen, Muthy, Zaynah, Sudlow, Cathie, Peto, Tunde, Peng Tee Khaw, and Foster, Paul J.

Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2019
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43. Failed Trabeculectomy

Author

Celso A Tello, Iqbal Ike K Ahmed, and Peng Tee Khaw

Subjects
Male, Reoperation, Fistula, Antimetabolites, Mitomycin, Trabeculectomy, Middle Aged, Tonometry, Ocular, Ophthalmology, Humans, Fluorouracil, Treatment Failure, Glaucoma Drainage Implants, Conjunctiva, Glaucoma, Open-Angle, Intraocular Pressure
Published
2005

44. Advances in Glaucoma Surgery: Evolution of Antimetabolite Adjunctive Therapy

Author

Sir Peng Tee Khaw

Subjects
medicine.medical_specialty, Antimetabolites, medicine.drug_class, business.industry, Mitomycin, medicine.medical_treatment, Glaucoma, medicine.disease, Antimetabolite, Intraoperative Period, Ophthalmology, Chemotherapy, Adjuvant, medicine, Glaucoma surgery, Humans, Optometry, Fluorouracil, business
Published
2001

45. Focus on molecules: neural retina leucine zipper (NRL)

Author

Hari Jayaram, Peng-Tee Khaw, G. Astrid Limb, and Robert E MacLaren

Subjects
Leucine zipper, Zipper, retinal development, Chemistry, Protein subunit, Retinal Degeneration, photoreceptor, Sensory Systems, Retina, Cell biology, DNA binding site, Ophthalmology, Cellular and Molecular Neuroscience, Mice, Basic-Leucine Zipper Transcription Factors, Recognition sequence, Transcription (biology), Retinal Rod Photoreceptor Cells, Animals, Humans, NRL, Eye Proteins, Transcription factor, Alpha helix, Transcription Factors
Abstract

The protein NRL (neural retina leucine zipper) (Uniprot Accession #P54845) is a basic motif-leucine zipper (bZIP) transcription factor of theMaf sub-family, involved in cellular differentiation and gene regulation, that has an essential intrinsic role in the development of rod photoreceptors (Mears et al., 2001 (cited within Nichols et al., 2010)). The gene is located on human chromosome 14q between bands 11.1 to 11.2 and encodes for a 237 amino acid proteinwith a molecular weight of 26 kDa that is located within the cellular nucleus. The leucine zipper domain is located between positions 187e208 (Fig. 1), with characteristic intertwined alpha helices forming a coil leading to a bifurcation at the DNA binding sites. The NRL protein is able to dimerise, forming both homoand heterodimers. The dimerisation composition influences DNA binding, with each dimer subunit independently able to recognise one half of the recognition sequence, leading to increased binding specificity and control of transcription. The additional DNA binding site in the NRL protein is provided by a basic domain located between positions 159e185 (Fig. 1A) on the amino terminal side of the domain.

Published
2012

46. Glaucoma Surgery

Author

Mark Wilkins, Paolo Bettin, and Sir Peng Tee Khaw

Published
2012

47. Modulation of wound healing during and after glaucoma surgery

Author

Stelios, Georgoulas, Annegret, Dahlmann-Noor, Stephen, Brocchini, and Peng Tee, Khaw

Subjects
Inflammation, Dendrimers, Wound Healing, Antibiotics, Antineoplastic, Neovascularization, Pathologic, Mitomycin, Glaucoma, Trabeculectomy, Fibroblasts, Cicatrix, Filtering Surgery, Humans, Immunologic Factors, Regeneration, Intraocular Pressure
Abstract

Following all types of glaucoma filtration surgery (GFS), scarring still poses the major threat to long-term success. The healing and scarring determine the percentage of patients achieving low final intraocular pressures (IOPs) that are associated with virtually no glaucoma progression. The use of antifibrotic agents to inhibit scarring of trabeculectomy blebs is now a well-established clinical practice. Unfortunately, severe complications such as leakage, infection, hypotony, and endophthalmitis with complete loss of vision may occur. In addition, surgery still fails in some individuals despite maximal doses of current antifibrotics. Better therapeutic agents are needed. Many promising new agents are being evaluated clinically and in vitro. In this chapter, we will discuss our current understanding of the wound healing process after glaucoma surgery and promising new treatment modalities.

Published
2008

48. Modulation of wound healing during and after glaucoma surgery

Author

Annegret Dahlmann-Noor, Stelios Georgoulas, Stephen Brocchini, and Peng Tee Khaw

Subjects
medicine.medical_specialty, Intraocular pressure, genetic structures, business.industry, medicine.medical_treatment, Glaucoma, medicine.disease, eye diseases, Surgery, Clinical Practice, Endophthalmitis, Filtration surgery, medicine, Glaucoma surgery, Trabeculectomy, sense organs, Wound healing, business
Abstract

Following all types of glaucoma filtration surgery (GFS), scarring still poses the major threat to long-term success. The healing and scarring determine the percentage of patients achieving low final intraocular pressures (IOPs) that are associated with virtually no glaucoma progression. The use of antifibrotic agents to inhibit scarring of trabeculectomy blebs is now a well-established clinical practice. Unfortunately, severe complications such as leakage, infection, hypotony, and endophthalmitis with complete loss of vision may occur. In addition, surgery still fails in some individuals despite maximal doses of current antifibrotics. Better therapeutic agents are needed. Many promising new agents are being evaluated clinically and in vitro. In this chapter, we will discuss our current understanding of the wound healing process after glaucoma surgery and promising new treatment modalities.

Published
2008

49. List of Contributors

Author

Juan-Carlos Abad, Mark B Abelson, David H Abramson, Martin A Acquadro, Anthony P Adamis, Wesley H Adams, Natalie A Afshari, Everett Ai, Lloyd M Aiello, Lloyd P Aiello, Levent Akduman, Marissa L Albano, Daniel M. Albert, Terry J Alexandrou, Eduardo C Alfonso, Jorge L Alié, Hassan Alizadeh, Ibrahim A Al Jadaan, Sabah Al-Jastaneiah, Calliope E Allen, David Allen, Robert C Allen, Albert Alm, Samar Al-Swailem, Abigail K Alt, Michael M Altaweel, Russell Anderson, Christopher M Andreoli, Sofia Androudi, Leonard PK Ang, Fahd Anzaar, David J Apple, Claudia A Arrigg, Pablo Artal, Penny Asbell, George K Asdourian, Neal Atebara, Pelin Atmaca-Sonmez, Isabelle Audo, Gerd U Auffarth, Robin K Avery, Dimitri T Azar, Ann S Baker, Mark Balles, Scott D Barnes, Donald M Barnett, Neal P Barney, Fina C Barouch, George B Bartley, Jason JS Barton, Irmgard Behlau, Jose I Belda, Jeffrey L Bennett, Timothy J Bennett, Gregg J Berdy, Carlo Roberto Bernardino, Vitaliano Bernardino, Eliot L Berson, Amitabh Bharadwaj, Robert Bhisitkul, Ravinder D Bhui, Jurij Bilyk, Valérie Biousse, Alan C Bird, Norman Paul Blair, Barbara A Blodi, Mark S Blumenkranz, H Culver Boldt, Mark S Borchert, Luigi Borrillo, Gary E Borodic, S Arthur Boruchoff, Swaraj Bose, Michael E Boulton, RW Bowman, Elizabeth A Bradley, Periklis D Brazitikos, Robert Breeze, Neil M Bressler, Susan B Bressler, Alfred Brini, Donald L Budenz, Angela N Buffenn, Scott E Burk, Salim Butrus, David Callanan, J Douglas Cameron, Louis B Cantor, William A Cantore, Jorge Cantu-Dibildox, Victoria Casas, Miriam Casper, Robin J Casten, Yara P Catoira, Jerry Cavallerano, Samantha J Chai, Maria R Chalita, Sherman M Chamberlain, Audrey S Chan, Chi-Chao Chan, Paul Chan, Matthew J Chapin, Karen L Chapman, Eric Chen, Joe Chen, Julie A Chen, Teresa C Chen, Zhou Chen, Patricia Chévez-Barrios, Emily Y Chew, Mark Chiang, James Chodosh, Eva-Marie Chong, Denise Chun, Leo T Chylack, Antonio P Ciardella, Mortimer Civan, Liane Clamen, John I Clark, Glenn Cockerham, Andre Cohen, Elisabeth J Cohen, Kathryn A Colby, Anne L Coleman, Hanna R Coleman, Joseph Colin, J Michael Collier, Grant M Comer, M Ronan Conlon, Kim E Cooper, James J Corbett, Miguel C Coma, Marshall N Cyrlin, Linda R Dagi, Matthew A Dahlgren, Timothy J Daley, Andrea P Da Mata, Bertil Damato, Donald J D'Amico, Reza Dana, Aude Danan-Husson, Helen B Danesh-Meyer, Ronald P Danis, Jason K Darlington, Stefanie L Davidson, Janet L Davis, Elizabeth A Davis, Jose J de la Cruz, Adam G de la Garza, Margaret M DeAngelis, Sheri L DeMartelaere, Joseph L Demer, Avninder Dhaliwal, J Paul Dieckert, Diana V Do, Marshall G Doane, Christopher Dodds, Claes H Dohlman, Guy Donati, Eric D Donnenfeld, Arlene Drack, Thaddeus P Dryja, David Dueker, Jay S Duker, Jennifer A Dunbar, James P Dunn, William J Dupps, Marlene L Durand, Jonathan J Dutton, Chiara M Eandi, Deepak P Edward, Robert A Egan, David A Eichenbaum, Susan E Eklund, Elizabeth C Engle, Kristine Erickson, Bita Esmaeli, Aaron Fay, Leonard Feiner, Sharon Fekrat, Frederick L Ferris, Howard F Fine, Donald C Fletcher, Paul Flikier, Richard P Floyd, Harry W Flynn, Donald S Fong, Ramon L Font, Brian JR Forbes, Rod Foroozan, Bradley S Foster, C Stephen Foster, Jill A Foster, Gary N Foulks, Tamara R Fountain, Gregory M Fox, Thomas F Freddo, Sharon F Freedman, K Bailey Freund, Thomas R Friberg, Alan H Friedman, David Friedman, Deborah I Friedman, Ephraim Friedman, Arthur D Fu, Anne B Fulton, Ahmed Galal, Steven Galetta, Mark Gallardo, Brenda Gallie, Alec Garner, James A Garrity, Damien Gatinel, Steven J Gedde, Craig E Geist, Steve Gerber, Ramon C Ghanem, Jon P Gieser, Michael S Gilmore, Howard V Gimbel, Ilene K Gipson, Tyrone Glover, Robert A Goldberg, Mordechai Goldenfeld, Scott M Goldstein, Cintia F Gomi, Haiyan Gong, John A Gonzales, John Goosey, Justin L Gottlieb, Joshua Gould, Evangelos S Gragoudas, David B Granet, Michael J Greaney, Daniel G Green, Franz Grehn, Jack V Greiner, Craig M Greven, Gregory J Griepentrog, Carl Groenewald, Cynthia L Grosskreutz, Lori Latowski Grover, Vamsi K Gullapalli, Padma Gulur, Jonathan Gunther, Manish Gupta, Mayank Gupta, David R Guyer, Darin R Haivala, Julia A Haller, GM Halmagyi, Lawrence S Halperin, Islam M Hamdi, Steven R Hamilton, Kristin M Hammersmith, Dennis P Han, Ronald M Hansen, J William Harbour, Seenu M Hariprasad, Mona Harissi-Dagher, Shirin E. Hassan, Mark P Hatton, Pamela Hawley, Yasutaka Hayashida, John R Heckenlively, Thomas R Hedges, Alfred D Heggie, Katrinka L Heher, Jeffrey S Heier, J Fielding Hejtmancik, Bonnie A Henderson, Peter S Hersh, Ahmed A Hidayat, Eva Juliet Higginbotham, Tatsuo Hirose, Allen C Ho, ThucAnh T Ho, R Nick Hogan, David E Holck, Nancy M Holekamp, Peter G Hovland, Thomas C Hsu, William C Hsu, Andrew JW Huang, Mark S Hughes, Jennifer Hui, David G Hunter, Laryssa A Huryn, Deeba Husain, Robert A Hyndiuk, Michael Ip, Brian J Jacobs, Frederick A Jakobiec, Lee M Jampol, Harold G Jensen, Fei Ji, David L Johnson, Douglas H Johnson, Mark W Johnson, R Paul Johnson, Robert N Johnson, Karen M Joos, Nancy C Joyce, J Michael Jumper, Ula V. Jurkunas, Alon Kahana, Malik Y Kahook, Elliott Kanner, Kevin Kalwerisky, Henry J Kaplan, Ekaterini C Karatza, Randy Kardon, James A Katowitz, William R Katowitz, Melanie Kazlas, Kelly S Keefe, Lara Kelley, Charles J Kent, Kenneth R Kenyon, Bilal F Khan, Jemshed A Khan, Naheed W Khan, Peng Tee Khaw, Femida Kherani, Eva C Kim, Hee Joon Kim, Ivana K Kim, Jonathan W Kim, Rosa Y Kim, Stella K Kim, Tae-Im Kim, Christina M Klais, Stephen R Klapper, Barbara EK Klein, Guy Kleinmann, Thomas Klink, Dino D Klisovic, Stephen D Klyce, Tolga Kocaturk, Thomas Kohnen, Takeshi Kojima, Tobias Koller, David A Kostick, Joel A Kraut, Chandrasekharan Krishnan, Ronald R Krueger, Joseph H Krug, Sara Krupsky, Rachel W Kuchtey, Ramsay S Kurban, Paul A Kurz, JR Kuszak, Young H Kwon, Thad A Labbe, Deborah L Lam, Jeffrey C Lamkin, Kathleen A Lamping, Anne Marie Lane, Katherine A Lane, Keith J Lane, Jonathan H Lass, Mary G Lawrence, Andrew G Lee, Carol M Lee, Michael S Lee, Paul P Lee, William B Lee, Igal Leibovitch, Bradley N Lemke, Craig A Lemley, Andrea Leonardi, Simmons Lessell, Leonard A Levin, Grace A Levy-Clarke, Julie C Lew, Craig Lewis, Wei Li, Laurence S Lim, Lyndell L Lim, Wee-Kiak Lim, Grant T Liu, John I Loewenstein, McGregor N Lott, Jonathan C Lowry, David B Lyon, Robert E Lytle, Mathew MacCumber, Bonnie T Mackool, Nalini A Madiwale, Francis Mah, Martin A Mainster, Michael H Manning, Steven L Mansberger, Robert E Marc, Mellone Marchong, Dennis M Marcus, Julie A Mares, Brian P Marr, Carlos E Martinez, Robert W Massof, Yukihiro Matsumoto, Cynthia Mattox, Marlon Maus, Cathleen M McCabe, Steven A McCormick, Michael McCrakken, James P McCulley, John A McDermott, H Richard McDonald, Marguerite B McDonald, Peter J McDonnell, Robert McGillivray, Craig A McKeown, James McLaughlin, W Wynn McMullen, Shlomo Melamed, George Meligonis, Efstratios Mendrinos, Dale R Meyer, Catherine B Meyerle, William F Mieler, Michael Migliori, Martin C Mihm, Darlene Miller, David Miller, Joan W Miller, Neil R Miller, David M Mills, Monte D Mills, Tatyana Milman, Lylas Mogk, Marja Mogk, Jordi Monés, Robert Montes-Micó, Christie L Morse, Asa D Morton, Anne Moskowitz, Shizuo Mukai, A Linn Murphree, Robert P Murphy, Timothy G Murray, Philip I Murray, Karina Nagao, Jay Neitz, Maureen Neitz, Peter A Netland, Arthur H Neufeld, Nancy J Newman, Eugene WM Ng, Quan Dong Nguyen, Jerry Y Niederkorn, Robert J Noecker, Robert B Nussenblatt, Joan M O'Brien, Paul D O'Brien, Terrence P O'Brien, Denis O'Day, R Joseph Olk, Karl R Olsen, Sumru Onal, Yen Hoong Ooi, E Mitchel Opremcak, George Ousler, Randall R Ozment, Samuel Packer, Millicent L Palmer, George N Papaliodis, DJ John Park, David W Parke, Cameron F Parsa, M Andrew Parsons, Louis R Pasquale, Neha N Patel, Sayjal J Patel, Thomas D Patrianakos, James R Patrinely, Deborah Pavan-Langston, Eli Peli, Susan M Pepin, Victor L Perez, Juan J Pérez-Santonja, John R Perfect, Henry D Perry, Joram Piatigorsky, Dante Pieramici, Eric A Pierce, Roberto Pineda, Misha L Pless, Howard D Pomeranz, Constantin J Pournaras, William Power, Manvi Prakash, Anita G Prasad, Valerie Purvin, David A Quillen, Graham E Quinn, Melvin D Rabena, James L Rae, Michael B Raizman, Alessandro Randazzo, Narsing A Rao, Christopher J Rapuano, Sherman W Reeves, Carl D Regillo, Elias Reichel, Martin H Reinke, Douglas Rhee, Claudia U Richter, Joseph F Rizzo, Richard M Robb, Anja C Roden, I Rand Rodgers, Merlyn M Rodrigues, Yonina Ron, Geoffrey E Rose, Emanuel S Rosen, James T Rosenbaum, Perry Rosenthal, Strutha C Rouse, Barry W Rovner, Malgorzata Rozanowska, Michael P Rubin, Peter AD Rubin, Shimon Rumelt, Anil K Rustgi, Tina Rutar, Mark S Ruttum, Allan R Rutzen, Edward T Ryan, Alfredo A Sadun, José-Alain Sahel, Leorey Saligan, Sarwat Salim, John F Salmon, Diva R Salomão, David Sami, Michael A Sandberg, Virender S Sangwan, Maria A Saornil, Joseph W Sassani, Rony R Sayegh, Andrew P Schachat, Wiley A Schell, Amy C Schefler, Tina Scheufele, Vivian Schiedler, Gretchen Schneider, Alison Schroeder, Ronald A Schuchard, Joel S Schuman, Ivan R Schwab, Adrienne Scott, Ingrid U Scott, Marvin L Sears, Johanna M Seddon, Theo Seiler, Robert P Selkin, Richard D Semba, Irina Serbanescu, Briar Sexton, Tarek M Shaarawy, Peter Shah, Aron Shapiro, Savitri Sharma, Jean Shein, Debra J Shetlar, M Bruce Shields, Carol L Shields, Jerry A Shields, Bradford J Shingleton, John W Shore, Lesya M Shuba, Guy J Ben Simon, Richard J Simmons, Michael Simpson, Arun D Singh, Omah S Singh, Karen Sisley, Arthur J Sit, David Smerdon, William E Smiddy, Ronald E Smith, Terry J Smith, Neal G Snebold, Lucia Sobrin, John A Sorenson, Sarkis H Soukiasian, George L Spaeth, Richard F Spaide, Monika Srivastava, Sunil K Srivastava, Alexandros N Stangos, Tomy Starck, Walter J Stark, Joshua D Stein, Roger F Steinert, Leon Strauss, Barbara W Streeten, J Wayne Streilein, James D Strong, Ilene K Sugino, Eric B Suhler, Timothy J Sullivan, Jennifer K Sun, Janet S Sunness, Francis C Sutula, Nasreen A Syed, Christopher N Ta, Hidehiro Takei, Jonathan H Talamo, Richard R Tamesis, Madhura Tamhankar, Kristen J Tarbet, Michelle Tarver-Carr, Mark A Terry, Joseph M Thomas, Vance Thompson, Jennifer E Thorne, Matthew J Thurtell, David P Tingey, King W To, Faisal M Tobaigy, Michael J Tolentino, Melissa G Tong, Gail Torkildsen, Cynthia A Toth, Elias I Traboulsi, Michele Trucksis, James C Tsai, Julie H Tsai, David T Tse, Scheffer CG Tseng, Elmer Y Tu, Ira J Udell, Alejandra A Valenzuela, Russell N Van Gelder, Gregory P Van Stavern, Deborah K Vander Veen, Demetrios Vavvas, David H Verity, Paolo Vinciguerra, Paul F Vinger, Nicholas J Volpe, Werner Wackernagel, Sonal Desai Wadhwa, Michael D Wagoner, Nadia K Waheed, David S Walton, Martin Wand, Jie Jin Wang, Scott M Warden, Lennox Webb, David Weber, Daniel Wee, Corey B Westerfeld, Christopher T Westfall, Scott M Whitcup, Valerie A White, William L White, Jason Wickens, Janey L Wiggs, Jacob T Wilensky, Charles P Wilkinson, Patrick D Williams, David J Wilson, M Roy Wilson, Steven E Wilson, Jules Winokur, William J Wirostko, Gadi Wollstein, Albert Chak Ming Wong, Tien Y Wong, John J Woog, Michael Wride, Carolyn S Wu, Darrell WuDunn, Jean Yang, Lawrence A Yannuzzi, Michael J Yaremchuk, R Patrick Yeatts, Richard W Yee, Steven Yeh, Lucy HY Young, Jenny Y Yu, Beatrice YJT Yue, Charles M Zacks, Bruce M Zagelbaum, Maryam Zamani, Marco Zarbin, Leonidas Zografos, and Christopher I Zoumalan

Published
2008

50. CONTRIBUTORS

Author

Richard L. Abbott, Natalie A. Afshari, Jaya Agrawal, Shishir Agrawal, Trilok P. Agrawal, Levent Akduman, Esen K. Akpek, Amal Al-Sayyed, Thomas A. Albini, Deborah M. Alcorn, Amar Alwitry, Anouk Amzel, Nicole J. Anderson, Ejaz A. Ansari, Andrew Antoszyk, James H. Antoszyk, James V. Aquavella, Sumaira A. Arain, J. Fernando Arévalo, Guruswami Arunagiri, Carlos W. Arzabe, La-ongsri Atchaneeyasakul, Huban Atilla, Ümit Aykan, Brandon D. Ayres, Juan J. Barbón, Kristi Bailey, Frank G. Baloh, Irina S. Barequet, André Barkhuizen, Michael A. Bearn, Rubens Belfort, A. Robert Bellows, Audina M. Berrocal, Marijke Wefers Bettink-Remeijer, Anuja Bhandari, M. Tariq Bhatti, Mark S. Blumenkranz, Kostas G. Boboridis, James P. Bolling, Vivien Boniuk, Paul Jorge Botelho, Paul W. Brazis, Fion D. Bremner, Edward G. Buckley, John D. Bullock, David Matthew Bushley, Jorge Alberto F. Caldeira, Anne Carricajo, Gian Maria Cavallini, Matilda Frances Chan, Damon B. Chandler, H. Channa, Devron H. Char, Steve Charles, Teresa C. Chen, Steven S.T. Ching, Christophe Chiquet, Phillip Hyunchul, Timothy Y. Chou, Stephen P. Christiansen, Kelly D. Chung, George A. Cioffi, Michael P. Clarke, David K. Coats, Elisabeth J. Cohen, R. Max Conway, Catherine Creuzot-Garcher, Emmett T. Cunningham, Theodore H. Curtis, Roger A. Dailey, Richard M. Davis, Romain De Cock, Jan-Tjeerd H.N. de Faber, Daniel de la Mano, Nick W.H.M. Dekkers, Monte Anthony Del Monte, David A. Della Rocca, Robert C. Della Rocca, Deepinder K. Dhaliwal, Diana V. Do, Peter J. Dolman, Sean P. Donahue, Eric D. Donnenfeld, Graham Duguid, Jay S. Duker, James P. Dunn, Steven P. Dunn, Hon-Vu Q. Duong, Robert A. Egan, Michael D. Eichler, Mays El-Dairi, Forrest J. Ellis, Geoffrey Emerson, M. Vaughn Emerson, Laura B. Enyedi, Teodoro Evans, Julie Falardeau, Bishara M. Faris, Marianne E. Feitl, Warren L. Felton, Stephen S. Feman, Timothy J ffytche, Christina J. Flaxel, Rod Foroozan, Allen Foster, Frederick T. Fraunfelder, Frederick W. Fraunfelder, H. Mackenzie Freeman, Mitchell H. Friedlaender, Larry P. Frohman, Wayne E. Fung, Philippe Gain, Jaime R. Gaitan, Stephen Gancher, Tim Gard, Devin M. Gattey, Peter L. Gehlbach, Mehdi Ghajarnia, Vinícius Coral Ghanem, Amit Kumar Ghosh, Chandak Ghosh, Matthew Giegengack, Geoffrey Gladstone, Daniel H. Gold, Richard L. Golub, Dan S. Gombos, George M. Gombos, William V. Good, Shawn Goodman, John D. Gottsch, Srinivas Goverdhan, Baird S. Grimson, Adolfo Güemes, Roberto Guerra, Julia A. Haller, Kristin M. Hammersmith, Irvin L. Handelman, Roderick N. Hargrove, Michael S. Harney, Richard A. Harper, Sarah R. Hatt, Barbara S. Hawkins, Sohan S. Hayreh, Arnd Heiligenhaus, Carsten Heinz, Leon W. Herndon, Simon J. Hickman, Koji Hirano, Edward J. Holland, Gary N. Holland, Eric R. Holz, Sachiko Hommura, Jeffrey D. Horn, Richard B. Hornick, H. Dunbar Hoskins, James W. Hung, Brian A. Hunter, Krista A. Hunter, Alex P. Hunyor, Brian Hurwitz, Thomas S. Hwang, Robert A. Hyndiuk, Ozge Ilhan-Sarac, Edsel Ing, Masanori Ino-ue, Carlos M. Isada, Saylin Iturriaga, Joseph D. Iuorno, Andrew G. Iwach, Mohan N. Iyer, Natalio J. Izquierdo, Lee M. Jampol, Suzanne Johnston, Sibel Kadayifçilar, Ian H. Kaden, Dieudonne Kaimbo Wa Kaimbo, Rashmis Kapur, Peter R. Kastl, Garyfallia Katsavounidou, Ayat Kazerouni, Michael Kazim, Sanjay R. Kedhar, Ronald V. Keech, Robert C. Kersten, Marshall P. Keys, Sangeeta Khanna, Peng Tee Khaw, James L. Kinyoun, Caitriona Kirwan, Tero Kivelä, Michael L. Klein, Stephen A. Klotz, John Ko, Regis P. Kowalski, Jay H. Krachmer, Theodore Krupin, Ferenc Kuhn, Abhaya Vivek Kulkarni, Robert C. Kwun, Peter R. Laibson, Rohit R. Lakhanpal, Byron L. Lam, Laurent Lamer, David P. Lawlor, Andrew W. Lawton, Alan B. Leahey, Russell LeBoyer, Andrew G. Lee, Wen-Hsiang Lee, William Barry Lee, Sharon S. Lehman, Howard M. Leibowitz, James Leong, Alex V. Levin, Leonard A. Levin, Mark R. Levine, Norman S. Levy, Thomas J. Liesegang, Lyndell L. Lim, Linda H. Lin, Richard D. Lisman, David Litoff, James C. Liu, Evan Loft, Ronald R. Lubritz, David C.W. Mabey, Ian A. Mackie, Srilakshmi Maguluri, M. Maliki, Nick Mamalis, Mark J. Mannis, Steven L. Mansberger, Ahmad M. Mansour, Alexandre S. Marcon, Italo M. Marcon, Peter B. Marsh, Rookaya Mather, William D. Mathers, K. Matti Saari, Louise A. Mawn, Penny J. McAllum, Rex M. McCallum, Peter McCluskey, Gregory J. McCormick, Steven A. McCormick, James P. McCulley, John G. McHenry, Alan A. McNab, Jared J. Mee, Douglas L. Meier, David M. Meisler, Saul C. Merin, Dale R. Meyer, Roger F. Meyer, Kevin S. Michels, Tatyana Milman, Roni Mintz, Chantal F Morel, William R. Morris, Mark L. Moster, John Mourani, Cristina Muccioli, Raghu C. Mudumbai, Fernando H. Murillo-Lopez, Shoib Myint, Parveen K Nagra, A Naoumi, John Nassif, Michelle T. Nee, Marcelo V. Netto, John D. Ng, Hau T. Nguyen, Quan Dong Nguyen, Denis M. O'Day, A. Justin O'Day, Henry S. O'Halloran, Michael O'Keefe, Fumiki Okamoto, Richard J. Olson, James C. Orcutt, Sema Oruc Dundar, Aaron Osbourne, Maristela Amaral Palazzi, Earl A. Palmer, Maria Papadopoulos, Jeffrey R. Parnell, Cameron F. Parsa, Sanjay V. Patel, Emily Patterson, Scott D. Pendergast, Henry D. Perry, Keith Roberson Peters, Stephanie M. Po, Russell Pokroy, Allen Michael Putterman, Rubén Queiro, Nastaran Rafiei, Bahram Rahmani, Christopher J Rapuano, Karim Rasheed, S.R. Rathinam, Lawrence A. Raymond, Russell W. Read, August Lafayette, Franco M. Recchia, James J. Reidy, Adam C. Reynolds, Larry F. Rich, Robert Ritch, Richard M. Robb, Pierre-Yves Robert, Joseph E. Robertson, Shiyoung Roh, Jean-Paul Romanet, Jack Rootman, Barbara L. Roque, Manolette R. Roque, Arthur L. Rosenbaum, James Todd Rosenbaum, F. Hampton Roy, Paul A. Rundle, Alfredo A. Sadun, Norman A. Saffra, Sarwat Salim, John R. Samples, Alvina Pauline D Santiago, David A. Saperstein, Richard A. Saunders, James A. Savage, Tina A. Scheufele, Vivian Schiedler, Thomas K. Schlesinger, Abraham Schlossman, Lee K. Schwartz, Ingrid U. Scott, Jennifer Scruggs, Ernesto I. Segal, Ismail A. Shalaby, Aziz Sheikh, John D. Sheppard, Mark D. Sherman, Carol L. Shields, Jerry A. Shields, Amarpreet Singh, Christopher N. Singh, Eric L. Singman, Donna Siracuse-Lee, Aaron D. Smalley, Patricia W. Smith, Anthony W. Solomon, Hassane Souhail, Daniel H. Spitzberg, Thomas C. Spoor, Robert L. Stamper, Walter J. Stark, Eric A. Steele, Thomas L. Steinemann, Ann U. Stout, J. Timothy Stout, R. Doyle Stulting, Alan Sugar, Joel Sugar, Donny W. Suh, Eric B. Suhler, John H. Sullivan, John Everett Sutphin, Kenneth C. Swan, Khalid F. Tabbara, Mandeep S. Tamber, Angelo P. Tanna, Sinan Tatlipinar, Ramin Tayani, Klaus D. Teichmann, Mark A. Terry, Clement Chee Yung Tham, A. Therzaz, Gilles Thuret, Christopher Graham Tinley, Andrea C. Tongue, Rodrigo J. Torres, Robert N. Tower, Elias I Traboulsi, Rupan Trikha, Brenda J. Tripathi, Ramesh C. Tripathi, Ilknur Tugal-Tutkun, Irene Tung, Judith A. M. Van Evendingen, Jean D. Vaudaux, Niteen S Wairagkar, Joseph D. Walrath, Rory McConn Walsh, David S. Walton, Ronald E. Warwar, Peter G. Watson, John J. Weiter, Richard G. Weleber, Fleming D. Wertz, Igor Westra, David T. Wheeler, Charles P. Wilkinson, David J. Wilson, M. Edward Wilson, Matthew W. Wilson, Steven E Wilson, John L. Wobig, Terry D. Wood, Lihteh Wu, Ozgur Yalcinbayir, Howard Shann-Cherng Ying, Peter N. Youssef, and Gerald W. Zaidman

Published
2008

Catalog

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